Recombinant and chimeric KS1/4 antibodies directed against a human adenocarcinoma antigen

• US 4,975,369 A
• Filed: 04/21/1988
• Issued: 12/04/1990
• Est. Priority Date: 04/21/1988
• Status: Expired due to Fees

• Current Assignee: Eli Lilly and Company
• Original Assignee: Eli Lilly and Company
• Inventors: Bumol, Thomas F., Gadski, Robert A., Beavers, Lisa S., Weigel, Barbara J.
• Primary Examiner(s): Schwartz, Richard A.
• Assistant Examiner(s): Marks, Michelle S.
• Application Number:
  US07/184,522
• Time in Patent Office: 957 Days
• Field of Search: 435/68, 435/70, 435/172.3, 435/235, 435/320, 435/240.1, 435/69.1, 536/27, 530/387, 935/70, 935/71
• US Class Current: 435/69.1
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07K 16/30 from tumour cells
• CPC Class Codes: C07K 16/462 Igs containing a variable region (Fv) from one specie and a constant region (Fc) from another
• CPC Class Codes: C07K 2317/24 containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2319/02 containing a signal sequence
• CPC Class Codes: C07K 2319/33 fusions for targeting to specific cell types, e.g. tissue specific targeting, targeting of a bacterial subspecies
• CPC Class Codes: Y10S 530/867 involving immunoglobulin or antibody produced via recombinant dna technology

Abstract

The present invention comprises novel recombinant DNA compounds which encode monoclonal antibody KS1/4 and chimeric derivatives of monoclonal antibody KS1/4. Eukaryotic expression vectors have been constructed that comprise novel KS1/4-encoding DNA and drive expression of KS1/4 when transformed into an appropriate host cell. The novel expression vectors can be used to create modified and chimeric derivatives of KS1/4. The recombinant-produced KS1/4, KS1/4 derivatives and KS1/4 chimeras are useful for the diagnosis, prognosis and treatment of disease states including adenocarcinoma.

Claims

1. A recombinant DNA compound that comprises DNA encoding an antibody light chain with the amino acid residue sequence consisting essentially of:

space="preserve" listing-type="tabular">__________________________________________________________________________ Gln Ile Leu Leu Thr Gln Ser Pro Ala Ile Met Ser Ala Ser Pro Gly Glu Lys Val Thr Met Thr Cys Ser Ala Ser Ser Ser Val Ser Tyr Met Leu Trp Tyr Gln Gln Lys Pro Gly Ser Ser Pro Lys Pro Trp Ile Phe Asp Thr Ser Asn Leu Ala Ser Gly Phe Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Ser Tyr Ser Leu Ile Ile Ser Ser Met Glu Ala Glu Asp Ala Ala Thr Tyr Tyr Cys His Gln Arg Ser Gly Tyr Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg Ala Asp Ala Ala Pro Thr Val Ser Ile Phe Pro Pro Ser Ser Glu Gln Leu Thr Ser Gly Gly Ala Ser Val Val Cys Phe Leu Asn Asn Phe Tyr Pro Lys Asp Ile Asn Val Lys Trp Lys Ile Asp Gly Ser Glu Arg Gln Asn Gly Val Leu Asn Ser Trp Thr Asp Gln Asp Ser Lys Asp Ser Thr Tyr Ser Met Ser Ser Thr Leu Thr Leu Thr Lys Asp Glu Tyr Glu Arg His Asn Ser Tyr Thr Cys Glu Ala Thr His Lys Thr Ser Thr Ser Pro Ile Val Lys Ser Phe Asn Arg Asn Glu Cys __________________________________________________________________________

2. The recombinant DNA compound of claim 1 wherein the coding strand is:

space="preserve" listing-type="tabular">__________________________________________________________________________ CAA ATT CTT CTC ACC CAG TCT CCA GCA ATC ATG TCT GCA TCT CCA GGG GAG AAG GTC ACC ATG ACC TGC AGT GCC AGC TCA AGT GTA AGT TAC ATG CTC TGG TAC CAG CAG AAG CCA GGA TCC TCG CCC AAA CCC TGG ATT TTT GAC ACA TCC AAC CTG GCT TCT GGA TTC CCT GCT CGC TTC AGT GGC AGT GGG TCT GGG ACC TCT TAC TCT CTC ATA ATC AGC AGC ATG GAG GCT GAA GAT GCT GCC ACT TAT TAC TGC CAT CAG CGG AGT GGT TAC CCG TAC ACG TTC GGA GGG GGG ACC AAG CTG GAA ATA AAA CGG GCT GAT GCT GCA CCA ACT GTA TCC ATC TTC CCA CCA TCC AGT GAG CAG TTA ACA TCT GGA GGT GCC TCA GTC GTG TGC TTC TTG AAC AAC TTC TAC CCC AAA GAC ATC AAT GTC AAG TGG AAG ATT GAT GGC AGT GAA CGA CAA AAT GGC GTC CTG AAC AGT TGG ACT GAT CAG GAC AGC AAA GAC AGC ACC TAC AGC ATG AGC AGC ACC CTC ACG TTG ACC AAG GAC GAG TAT GAA CGA CAT AAC AGC TAT ACC TGT GAG GCC ACT CAC AAG ACA TCA ACT TCA CCC ATT GTC AAG AGC TTC AAC AGG AAT GAG TGT __________________________________________________________________________

3. A recombinant DNA compound that comprises DNA encoding an antibody light chain and the signal peptide of said light chain with the amino acid sequence consisting essentially of:

space="preserve" listing-type="tabular">__________________________________________________________________________ Met Asp Phe Gln Val Gln Ile Phe Ser Phe Leu Leu Ile Ser Ala Ser Val Ile Met Ser Arg Gly Gln Ile Leu Leu Thr Gln Ser Pro Ala Ile Met Ser Ala Ser Pro Gly Glu Lys Val Thr Met Thr Cys Ser Ala Ser Ser Ser Val Ser Tyr Met Leu Trp Tyr Gln Gln Lys Pro Gly Ser Ser Pro Lys Pro Trp Ile Phe Asp Thr Ser Asn Leu Ala Ser Gly Phe Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Ser Tyr Ser Leu Ile Ile Ser Ser Met Glu Ala Glu Asp Ala Ala Thr Tyr Tyr Cys His Gln Arg Ser Gly Tyr Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg Ala Asp Ala Ala Pro Thr Val Ser Ile Phe Pro Pro Ser Ser Glu Gln Leu Thr Ser Gly Gly Ala Ser Val Val Cys Phe Leu Asn Asn Phe Tyr Pro Lys Asp Ile Asn Val Lys Trp Lys Ile Asp Gly Ser Glu Arg Gln Asn Gly Val Leu Asn Ser Trp Thr Asp Gln Asp Ser Lys Asp Ser Thr Tyr Ser Met Ser Ser Thr Leu Thr Leu Thr Lys Asp Glu Tyr Glu Arg His Asn Ser Tyr Thr Cys Glu Ala Thr His Lys Thr Ser Thr Ser Pro Ile Val Lys Ser Phe Asn Arg Asn Glu Cys __________________________________________________________________________

4. The recombinant DNA compound of claim 3 wherein the coding strand is:

space="preserve" listing-type="tabular">__________________________________________________________________________ ATG GAT TTT CAA GTG CAG ATT TTT AGC TTC CTG CTA ATC AGT GCT TCA GTC ATA ATG TCC AGA GGA CAA ATT CTT CTC ACC CAG TCT CCA GCA ATC ATG TCT GCA TCT CCA GGG GAG AAG GTC ACC ATG ACC TGC AGT GCC AGC TCA AGT GTA AGT TAC ATG CTC TGG TAC CAG CAG AAG CCA GGA TCC TCG CCC AAA CCC TGG ATT TTT GAC ACA TCC AAC CTG GCT TCT GGA TTC CCT GCT CGC TTC AGT GGC AGT GGG TCT GGG ACC TCT TAC TCT CTC ATA ATC AGC AGC ATG GAG GCT GAA GAT GCT GCC ACT TAT TAC TGC CAT CAG CGG AGT GGT TAC CCG TAC ACG TTC GGA GGG GGG ACC AAG CTG GAA ATA AAA CGG GCT GAT GCT GCA CCA ACT GTA TCC ATC TTC CCA CCA TCC AGT GAG CAG TTA ACA TCT GGA GGT GCC TCA GTC GTG TGC TTC TTG AAC AAC TTC TAC CCC AAA GAC ATC AAT GTC AAG TGG AAG ATT GAT GGC AGT GAA CGA CAA AAT GGC GTC CTG AAC AGT TGG ACT GAT CAG GAC AGC AAA GAC AGC ACC TAC AGC ATG AGC AGC ACC CTC ACG TTG ACC AAG GAC GAG TAT GAA CGA CAT AAC AGC TAT ACC TGT GAG GCC ACT CAC AAG ACA TCA ACT TCA CCC ATT GTC AAG AGC TTC AAC AGG AAT GAG TGT __________________________________________________________________________

9. A recombinant DNA vector that comprises the DNA sequence of claim 3.

11. The recombinant DNA vector of claim 9 that is plasmid pGKC2310.

13. A recombinant DNA expression vector of claim 9 that further comprises a promoter and translational activating sequence positioned to drive expression of said DNA.

15. The recombinant DNA expression vector of claim 13, wherein said promoter is the Adenovirus Late Promoter.

5. A recombinant DNA compound that comprises DNA encoding an antibody heavy chain with the amino acid residue sequence consisting essentially of:

space="preserve" listing-type="tabular">__________________________________________________________________________ Gln Ile Gln Leu Val Gln Ser Gly Pro Glu Leu Lys Lys Pro Gly Glu Thr Val Lys Ile Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asn Tyr Gly Met Asn Trp Val Lys Gln Thr Pro Gly Lys Gly Leu Lys Trp Met Gly Trp Ile Asn Thr Tyr Thr Gly Glu Pro Thr Tyr Ala Asp Asp Phe Lys Gly Arg Phe Ala Phe Ser Leu Glu Thr Ser Ala Ser Thr Ala Phe Leu Gln Ile Gln Gln Pro Gln Asn Met Arg Thr Met Ala Thr Tyr Phe Cys Val Arg Phe Ile Ser Lys Gly Asp Tyr Trp Gly Gln Gly Thr Ser Val Thr Val Ser Ser Ala Lys Thr Thr Ala Pro Ser Val Tyr Pro Leu Ala Pro Val Cys Gly Asp Thr Thr Gly Ser Ser Val Thr Leu Gly Cys Leu Val Lys Gly Tyr Phe Pro Glu Pro Val Thr Leu Thr Trp Asn Ser Gly Ser Leu Ser Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Asp Leu Tyr Thr Leu Ser Ser Ser Val Thr Val Thr Ser Ser Thr Trp Pro Ser Gln Ser Ile Thr Cys Asn Val Ala His Pro Ala Ser Ser Thr Lys Val Asp Lys Lys Ile Glu Pro Arg Gly Pro Thr Ile Lys Pro Cys Pro Pro Cys Lys Cys Pro Ala Pro Asn Leu Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Ile Lys Asp Val Leu Met Ile Ser Leu Ser Pro Ile Val Thr Cys Val Val Val Asp Val Ser Glu Asp Asp Pro Asp Val Gln Ile Ser Trp Phe Val Asn Asn Val Glu Val His Thr Ala Gln Thr Gln Thr His Arg Glu Asp Tyr Asn Ser Thr Leu Arg Val Val Ser Ala Leu Pro Ile Gln His Gln Asp Trp Met Ser Gly Lys Glu Phe Lys Cys Lys Val Asn Asn Lys Asp Leu Pro Ala Pro Ile Glu Arg Thr Ile Ser Lys Pro Lys Gly Ser Val Arg Ala Pro Gln Val Tyr Val Leu Pro Pro Pro Glu Glu Glu Met Thr Lys Lys Gln Val Thr Leu Thr Cys Met Val Thr Asp Phe Met Pro Glu Asp Ile Tyr Val Glu Trp Thr Asn Asn Gly Lys Thr Glu Leu Asn Tyr Lys Asn Thr Glu Pro Val Leu Asp Ser Asp Gly Ser Tyr Phe Met Tyr Ser Lys Leu Arg Val Glu Lys Lys Asn Trp Val Glu Arg Asn Ser Tyr Ser Cys Ser Val Val His Glu Gly Leu His Asn His His Thr Thr Lys Ser Phe Ser Arg Thr Pro Gly Lys __________________________________________________________________________

6. The recombinant DNA compound of claim 5 wherein the coding strand is:

space="preserve" listing-type="tabular">__________________________________________________________________________ CAG ATC CAG TTG GTG CAG TCT GGA CCT GAG CTG AAG AAG CCT GGA GAG ACA GTC AAG ATC TCC TGC AAG GCT TCT GGG TAT ACC TTC ACA AAC TAT GGA ATG AAC TGG GTG AAG CAG ACT CCA GGA AAG GGT TTA AAG TGG ATG GGC TGG ATA AAC ACC TAC ACT GGA GAA CCA ACA TAT GCT GAT GAC TTC AAG GGA CGG TTT GCC TTC TCT TTG GAA ACC TCT GCC AGC ACT GCC TTT TTG CAG ATT CAA CAA CCT CAG AAT ATG AGG ACT ATG GCT ACA TAT TTC TGT GTA AGA TTT ATT TCT AAG GGG GAC TAC TGG GGT CAA GGA ACG TCA GTC ACC GTC TCC TCA GCC AAA ACA ACA GCC CCA TCG GTC TAT CCA CTG GCC CCT GTG TGT GGA GAT ACA ACT GGC TCC TCG GTG ACT CTA GGA TGC CTG GTC AAG GGT TAT TTC CCT GAG CCA GTG ACC TTG ACC TGG AAC TCT GGA TCC CTG TCC AGT GGT GTG CAC ACC TTC CCA GCT GTC CTG CAG TCT GAC CTC TAC ACC CTC AGC AGC TCA GTG ACT GTA ACC TCG AGC ACC TGG CCC AGC CAG TCC ATC ACC TGC AAT GTG GCC CAC CCG GCA AGC AGC ACC AAG GTG GAC AAG AAA ATT GAG CCC AGA GGG CCC ACA ATC AAG CCC TGT CCT CCA TGC AAA TGC CCA GCA CCT AAC CTC TTG GGT GGA CCA TCC GTC TTC ATC TTC CCT CCA AAG ATC AAG GAT GTA CTC ATG ATC TCC CTG AGC CCC ATA GTC ACA TGT GTG GTG GTG GAT GTG AGC GAG GAT GAC CCA GAT GTC CAG ATC AGC TGG TTT GTG AAC AAC GTG GAA GTA CAC ACA GCT CAG ACA CAA ACC CAT AGA GAG GAT TAC AAC AGT ACT CTC CGG GTG GTC AGT GCC CTC CCC ATC CAG CAC CAG GAC TGG ATG AGT GGC AAG GAG TTC AAA TGC AAG GTC AAC AAC AAA GAC CTC CCA GCG CCC ATC GAG AGA ACC ATC TCA AAA CCC AAA GGG TCA GTA AGA GCT CCA CAG GTA TAT GTC TTG CCT CCA CCA GAA GAA GAG ATG ACT AAG AAA CAG GTC ACT CTG ACC TGC ATG GTC ACA GAC TTC ATG CCT GAA GAC ATT TAC GTG GAG TGG ACC AAC AAC GGG AAA ACA GAG CTA AAC TAC AAG AAC ACT GAA CCA GTC CTG GAC TCT GAT GGT TCT TAC TTC ATG TAC AGC AAG CTG AGA GTG GAA AAG AAG AAC TGG GTG GAA AGA AAT AGC TAC TCC TGT TCA GTG GTC CAC GAG GGT CTG CAC AAT CAC CAC ACG ACT AAG AGC TTC TCC CGG ACT CCG GGT AAA __________________________________________________________________________

7. A recombinant DNA compound that comprises DNA encoding an antibody heavy chain and the signal peptide of said heavy chain with the amino acid sequence consisting essentially of:

space="preserve" listing-type="tabular">__________________________________________________________________________ Met Asp Trp Leu Trp Asn Leu Leu Phe Leu Met Ala Ala Ala Gln Ser Ala Gln Ala Gln Ile Gln Leu Val Gln Ser Gly Pro Glu Leu Lys Lys Pro Gly Glu Thr Val Lys Ile Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asn Tyr Gly Met Asn Trp Val Lys Gln Thr Pro Gly Lys Gly Leu Lys Trp Met Gly Trp Ile Asn Thr Tyr Thr Gly Glu Pro Thr Tyr Ala Asp Asp Phe Lys Gly Arg Phe Ala Phe Ser Leu Glu Thr Ser Ala Ser Thr Ala Phe Leu Gln Ile Gln Gln Pro Gln Asn Met Arg Thr Met Ala Thr Tyr Phe Cys Val Arg Phe Ile Ser Lys Gly Asp Tyr Trp Gly Gln Gly Thr Ser Val Thr Val Ser Ser Ala Lys Thr Thr Ala Pro Ser Val Tyr Pro Leu Ala Pro Val Cys Gly Asp Thr Thr Gly Ser Ser Val Thr Leu Gly Cys Leu Val Lys Gly Tyr Phe Pro Glu Pro Val Thr Leu Thr Trp Asn Ser Gly Ser Leu Ser Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Asp Leu Tyr Thr Leu Ser Ser Ser Val Thr Val Thr Ser Ser Thr Trp Pro Ser Gln Ser Ile Thr Cys Asn Val Ala His Pro Ala Ser Ser Thr Lys Val Asp Lys Lys Ile Glu Pro Arg Gly Pro Thr Ile Lys Pro Cys Pro Pro Cys Lys Cys Pro Ala Pro Asn Leu Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Ile Lys Asp Val Leu Met Ile Ser Leu Ser Pro Ile Val Thr Cys Val Val Val Asp Val Ser Glu Asp Asp Pro Asp Val Gln Ile Ser Trp Phe Val Asn Asn Val Glu Val His Thr Ala Gln Thr Gln Thr His Arg Glu Asp Tyr Asn Ser Thr Leu Arg Val Val Ser Ala Leu Pro Ile Gln His Gln Asp Trp Met Ser Gly Lys Glu Phe Lys Cys Lys Val Asn Asn Lys Asp Leu Pro Ala Pro Ile Glu Arg Thr Ile Ser Lys Pro Lys Gly Ser Val Arg Ala Pro Gln Val Tyr Val Leu Pro Pro Pro Glu Glu Glu Met Thr Lys Lys Gln Val Thr Leu Thr Cys Met Val Thr Asp Phe Met Pro Glu Asp Ile Tyr Val Glu Trp Thr Asn Asn Gly Lys Thr Glu Leu Asn Tyr Lys Asn Thr Glu Pro Val Leu Asp Ser Asp Gly Ser Tyr Phe Met Tyr Ser Lys Leu Arg Val Glu Lys Lys Asn Trp Val Glu Arg Asn Ser Tyr Ser Cys Ser Val Val His Glu Gly Leu His Asn His His Thr Thr Lys Ser Phe Ser Arg Thr Pro Gly Lys __________________________________________________________________________

8. The recombinant DNA compound of claim 7 wherein the coding strand is:

space="preserve" listing-type="tabular">__________________________________________________________________________ ATG GAT TGG CTG TGG AAC TTG CTA TTC CTG ATG GCA GCT GCC CAA AGT GCC CAA GCA CAG ATC CAG TTG GTG CAG TCT GGA CCT GAG CTG AAG AAG CCT GGA GAG ACA GTC AAG ATC TCC TGC AAG GCT TCT GGG TAT ACC TTC ACA AAC TAT GGA ATG AAC TGG GTG AAG CAG ACT CCA GGA AAG GGT TTA AAG TGG ATG GGC TGG ATA AAC ACC TAC ACT GGA GAA CCA ACA TAT GCT GAT GAC TTC AAG GGA CGG TTT GCC TTC TCT TTG GAA ACC TCT GCC AGC ACT GCC TTT TTG CAG ATT CAA CAA CCT CAG AAT ATG AGG ACT ATG GCT ACA TAT TTC TGT GTA AGA TTT ATT TCT AAG GGG GAC TAC TGG GGT CAA GGA ACG TCA GTC ACC GTC TCC TCA GCC AAA ACA ACA GCC CCA TCG GTC TAT CCA CTG GCC CCT GTG TGT GGA GAT ACA ACT GGC TCC TCG GTG ACT CTA GGA TGC CTG GTC AAG GGT TAT TTC CCT GAG CCA GTG ACC TTG ACC TGG AAC TCT GGA TCC CTG TCC AGT GGT GTG CAC ACC TTC CCA GCT GTC CTG CAG TCT GAC CTC TAC ACC CTC AGC AGC TCA GTG ACT GTA ACC TCG AGC ACC TGG CCC AGC CAG TCC ATC ACC TGC AAT GTG GCC CAC CCG GCA AGC AGC ACC AAG GTG GAC AAG AAA ATT GAG CCC AGA GGG CCC ACA ATC AAG CCC TGT CCT CCA TGC AAA TGC CCA GCA CCT AAC CTC TTG GGT GGA CCA TCC GTC TTC ATC TTC CCT CCA AAG ATC AAG GAT GTA CTC ATG ATC TCC CTG AGC CCC ATA GTC ACA TGT GTG GTG GTG GAT GTG AGC GAG GAT GAC CCA GAT GTC CAG ATC AGC TGG TTT GTG AAC AAC GTG GAA GTA CAC ACA GCT CAG ACA CAA ACC CAT AGA GAG GAT TAC AAC AGT ACT CTC CGG GTG GTC AGT GCC CTC CCC ATC CAG CAC CAG GAC TGG ATG AGT GGC AAG GAG TTC AAA TGC AAG GTC AAC AAC AAA GAC CTC CCA GCG CCC ATC GAG AGA ACC ATC TCA AAA CCC AAA GGG TCA GTA AGA GCT CCA CAG GTA TAT GTC TTG CCT CCA CCA GAA GAA GAG ATG ACT AAG AAA CAG GTC ACT CTG ACC TGC ATG GTC ACA GAC TTC ATG CCT GAA GAC ATT TAC GTG GAG TGG ACC AAC AAC GGG AAA ACA GAG CTA AAC TAC AAG AAC ACT GAA CCA GTC CTG GAC TCT GAT GGT TCT TAC TTC ATG TAC AGC AAG CTG AGA GTG GAA AAG AAG AAC TGG GTG GAA AGA AAT AGC TAC TCC TGT TCA GTG GTC CAC GAG GGT CTG CAC AAT CAC CAC ACG ACT AAG AGC TTC TCC CGG ACT CCG GGT AAA TGA GCT CAG CAC CCA CAA AAC TCT CAG GTC CAA AGA GAC ACC CAC __________________________________________________________________________

10. A recombinant DNA vector that comprises the DNA sequence of claim 7.

12. The recombinant DNA vector of claim 10 that is plasmid pG2A52.

14. A recombinant DNA expression vector of claim 10 that further comprises a promoter and translational activating sequence positioned to drive expression of said DNA.

16. The recombinant DNA expression vactor of claim 14, wherein said promoter is the Adenovirus Late Fromoter.

17. A recombinant DNA compound that comprises DNA encoding a chimeric antibody light chain comprising an antigen-specific variable region derived from a first mammalian species and a Constant region derived from a second and different mammalian species, said light chain variable region having an amino acid sequence consisting essentially of:

space="preserve" listing-type="tabular">__________________________________________________________________________ Gln Ile Leu Leu Thr Gln Ser Pro Ala Ile Met Ser Ala Ser Pro Gly Glu Lys Val Thr Met Thr Cys Ser Ala Ser Ser Ser Val Ser Tyr Met Leu Trp Tyr Gln Gln Lys Pro Gly Ser Ser Pro Lys Pro Trp Ile Phe Asp Thr Ser Asn Leu Ala Ser Gly Phe Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Ser Tyr Ser Leu Ile Ile Ser Ser Met Glu Ala Glu Asp Ala Ala Thr Tyr Tyr Cys His Gln Arg Ser Gly Tyr Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Gly __________________________________________________________________________

18. The recombinant DNA compound of claim 17 wherein the coding strand is:

space="preserve" listing-type="tabular">__________________________________________________________________________CAA ATT CTT CTC ACC CAG TCT CCA GCA ATC ATG TCT GCA TCT CCA GGG GAG AAG GTC ACC ATG ACC TGC AGT GCC AGC TCA AGT GTA AGT TAC ATG CTC TGG TAC CAG CAG AAG CCA GGA TCC TCG CCC AAA CCC TGG ATT TTT GAC ACA TCC AAC CTG GCT TCT GGA TTC CCT GCT CGC TTC AGT GGC AGT GGG TCT GGG ACC TCT TAC TCT CTC ATA ATC AGC AGC ATG GAG GCT GAA GAT GCT GCC ACT TAT TAC TGC CAT CAG CGG AGT GGT TAC CCG TAC ACG TTC GGA GGG GGG ACC AAG CTG GAA ATA AAA GGT __________________________________________________________________________

26. The recombinant DNA compound of claim 17 wherein the coding strand is:

space="preserve" listing-type="tabular">__________________________________________________________________________ CAG ATC CAG TTG GTG CAG TCT GGA CCT GAG CTG AAG AAG CCT GGA GAG ACA GTC AAG ATC TCC TGC AAG GCT TCT GGG TAT ACC TTC ACA AAC TAT GGA ATG AAC TGG GTG AAG CAG ACT CCA GGA AAG GGT TTA AAG TGG ATG GGC TGG ATA AAC ACC TAC ACT GGA GAA CCA ACA TAT GCT GAT GAC TTC AAG GGA CGG TTT GCC TTC TCT TTG GAA ACC TCT GCC AGC ACT GCC TTT TTG CAG ATT CAA CAA CCT CAG AAT ATG AGG ACT ATG GCT ACA TAT TTC TGT GTA AGA TTT ATT TCT AAG GGG GAC TAC TGG GGT CAA GGA ACG TCA GTC ACC GTC TCC TCA __________________________________________________________________________

29. A recombinant DNA vector that comprises the DNA sequence of claim 17, wherein the first DNA sequence is derived from a murine hybridoma.

35. The recombinant DNA vector of claim 29, wherein the second DNA sequence is derived from a human source.

19. A recombinant DNA compound that comprises DNA encoding a chimeric antibody light chain comprising an antigen-specific variable region and signal peptide derived from a first mammalian species and a constant region derived from a second and different mammalian species, said light chain variable region and signal peptide having an amino acid sequence consisting essentially of:

space="preserve" listing-type="tabular">__________________________________________________________________________ Met Asp Phe Gln Val Gln Ile Phe Ser Phe Leu Leu Ile Ser Ala Ser Val Ile Met Ser Arg Gly Gln Ile Leu Leu Thr Gln Ser Pro Ala Ile Met Ser Ala Ser Pro Gly Glu Lys Val Thr Met Thr Cys Ser Ala Ser Ser Ser Val Ser Tyr Met Leu Trp Tyr Gln Gln Lys Pro Gly Ser Ser Pro Lys Pro Trp Ile Phe Asp Thr Ser Asn Leu Ala Ser Gly Phe Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Ser Tyr Ser Leu Ile Ile Ser Ser Met Glu Ala Glu Asp Ala Ala Thr Tyr Tyr Cys His Gln Arg Ser Gly Tyr Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Gly __________________________________________________________________________

20. The recombinant DNA compound of claim 19 wherein the coding strand is:

space="preserve" listing-type="tabular">__________________________________________________________________________ ATG GAT TTT CAA GTG CAG ATT TTT AGC TTC CTG CTA ATC AGT GCT TCA GTC ATA ATG TCC AGA GGA CAA ATT CTT CTC ACC CAG TCT CCA GCA ATC ATG TCT GCA TCT CCA GGG GAG AAG GTC ACC ATG ACC TGC AGT GCC AGC TCA AGT GTA AGT TAC ATG CTC TGG TAC CAG CAG AAG CCA GGA TCC TCG CCC AAA CCC TGG ATT TTT GAC ACA TCC AAC CTG GCT TCT GGA TTC CCT GCT CGC TTC AGT GGC AGT GGG TCT GGG ACC TCT TAC TCT CTC ATA ATC AGC AGC ATG GAG GCT GAA GAT GCT GCC ACT TAT TAC TGC CAT CAG CGG AGT GGT TAC CCG TAC ACG TTC GGA GGG GGG ACC AAG CTG GAA ATA AAA GGT __________________________________________________________________________

30. A recombinant DNA vector that comprises the DNA sequence of claim 19, wherein the first DNA sequence is derived from a murine hybridoma.

36. The recombinant DNA vector of claim 30, wherein the second DNA sequence is derived from a human source.

41. The recombinant DNA vector of claim 36 that is plasmid CHKC2-18.

51. A recombinant DNA expression vector of claim 36 that further comprises a promoter and translational activating sequence positioned to drive expression of said DNA.

54. The recombinant DNA expression vector of claim 51 wherein said promoter is the Adenovirus Late Promoter.

21. A recombinant DNA compound that comprises DNA encoding a chimeric antibody light chain comprising an antigen-specific variable region derived from a first mammalian species and a constant region derived from a second and different mammalian species, said light chain variable region having an amino acid sequence consisting essentially of:

space="preserve" listing-type="tabular">__________________________________________________________________________ Gln Ile Leu Leu Thr Gln Ser Pro Ala Ile Met Ser Ala Ser Pro Gly Glu Lys Val Thr Met Thr Cys Ser Ala Ser Ser Ser Val Ser Tyr Met Leu Trp Tyr Gln Gln Lys Pro Gly Ser Ser Pro Lys Pro Trp Ile Phe Asp Thr Ser Asn Leu Ala Ser Gly Phe Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Ser Tyr Ser Leu Ile Ile Ser Ser Met Glu Ala Glu Asp Ala Ala Thr Tyr Tyr Cys His Gln Arg Ser Gly Tyr Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg __________________________________________________________________________

22. The recombinant DNA compound of claim 21 wherein the coding strand is:

space="preserve" listing-type="tabular">__________________________________________________________________________ CAA ATT CTT CTC ACC CAG TCT CCA GCA ATC ATG TCT GCA TCT CCA GGG GAG AAG GTC ACC ATG ACC TGC AGT GCC AGC TCA AGT GTA AGT TAC ATG CTC TGG TAC CAG CAG AAG CCA GGA TCC TCG CCC AAA CCC TGG ATT TTT GAC ACA TCC AAC CTG GCT TCT GGA TTC CCT GCT CGC TTC AGT GGC AGT GGG TCT GGG ACC TCT TAC TCT CTC ATA ATC AGC AGC ATG GAG GCT GAA GAT GCT GCC ACT TAT TAC TGC CAT CAG CGG AGT GGT TAC CCG TAC ACG TTC GGA GGG GGG ACC AAG CTG GAA ATA AAA CGT __________________________________________________________________________

31. A recombinant DNA vector that comprises the DNA sequence of claim 21, wherein the first DNA sequence is derived from a murine hybridoma.

37. The recombinant DNA vector of claim 31, wherein the second DNA sequence is derived from a human source.

23. A recombinant DNA compound that comprises DNA encoding a chimeric antibody light chain comprising an antigen-specific variable region and signal peptide derived from a first mammalian species and a constant region derived from a second and different mammalian species, said light chain variable region and signal peptide having an amino acid sequence consisting essentially of:

space="preserve" listing-type="tabular">__________________________________________________________________________ Met Asp Phe Gln Val Gln Ile Phe Ser Phe Leu Leu Ile Ser Ala Ser Val Ile Met Ser Arg Gly Gln Ile Leu Leu Thr Gln Ser Pro Ala Ile Met Ser Ala Ser Pro Gly Glu Lys Val Thr Met Thr Cys Ser Ala Ser Ser Ser Val Ser Tyr Met Leu Trp Tyr Gln Gln Lys Pro Gly Ser Ser Pro Lys Pro Trp Ile Phe Asp Thr Ser Asn Leu Ala Ser Gly Phe Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Ser Tyr Ser Leu Ile Ile Ser Ser Met Glu Ala Glu Asp Ala Ala Thr Tyr Tyr Cys His Gln Arg Ser Gly Tyr Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg __________________________________________________________________________

24. The recombinant DNA compound of claim 23 wherein the coding strand is:

space="preserve" listing-type="tabular">__________________________________________________________________________ ATG GAT TTT CAA GTG CAG ATT TTT AGC TTC CTG CTA ATC AGT GCT TCA GTC ATA ATG TCC AGA GGA CAA ATT CTT CTC ACC CAG TCT CCA GCA ATC ATG TCT GCA TCT CCA GGG GAG AAG GTC ACC ATG ACC TGC AGT GCC AGC TCA AGT GTA AGT TAC ATG CTC TGG TAC CAG CAG AAG CCA GGA TCC TCG CCC AAA CCC TGG ATT TTT GAC ACA TCC AAC CTG GCT TCT GGA TTC CCT GCT CGC TTC AGT GGC AGT GGG TCT GGG ACC TCT TAC TCT CTC ATA ATC AGC AGC ATG GAG GCT GAA GAT GCT GCC ACT TAT TAC TGC CAT CAG CGG AGT GGT TAC CCG TAC ACG TTC GGA GGG GGG ACC AAG CTG GAA ATA AAA CGT __________________________________________________________________________

32. A recombinant DNA vector that comprises the DNA sequence of claim 23, wherein the first DNA sequence is derived from a murine hybridoma.

38. The recombinant DNA vector of claim 32, wherein the second DNA sequence is derived from a human source.

42. The recombinant DNA vector of claim 38 that is plasmid CHKC2-6.

52. A recombinant DNA expression vector of claim 38 that further comprises a promoter and translational activating sequence positioned to drive expression of said DNA.

55. The recombinant DNA expression vector of claim 52 wherein said promoter is the Adenovirus Late Promoter.

25. A recombinant DNA compound that comprises DNA encoding a chimeric antibody heavy chain comprising an antigen specific variable region derived from a first mammalian species and a constant region derived from a second and different mammalian species, said heavy chain variable region having an amino acid sequence consisting essentially of:

space="preserve" listing-type="tabular">__________________________________________________________________________ Gln Ile Gln Leu Val Gln Ser Gly Pro Glu Leu Lys Lys Pro Gly Glu Thr Val Lys Ile Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asn Tyr Gly Met Asn Trp Val Lys Gln Thr Pro Gly Lys Gly Leu Lys Trp Met Gly Trp Ile Asn Thr Tyr Thr Gly Glu Pro Thr Tyr Ala Asp Asp Phe Lys Gly Arg Phe Ala Phe Ser Leu Glu Thr Ser Ala Ser Thr Ala Phe Leu Gln Ile Gln Gln Pro Gln Asn Met Arg Thr Met Ala Thr Tyr Phe Cys Val Arg Phe Ile Ser Lys Gly Asp Tyr Trp Gly Gln Gly Thr Ser Val Thr Val Ser Ser __________________________________________________________________________

33. A recombinant DNA vector that comprises the DNA sequence of claim 25, wherein the first DNA sequence is derived from a murine hybridoma.

39. The recombinant DNA vector of claim 33, wherein the second DNA sequence is derived from a human source.

27. A recombinant DNA compound that comprises DNA encoding a chimeric antibody heavy chain comprising an antigen-specific variable region and signal peptide derived from a first mammalian species and a constant region derived from a second and different mammalian species, said heavy chain variable region having an amino acid sequence consisting essentially of:

space="preserve" listing-type="tabular">__________________________________________________________________________ Met Asp Trp Leu Trp Asn Leu Leu Phe Leu Met Ala Ala Ala Gln Ser Ala Gln Ala Gln Ile Gln Leu Val Gln Ser Gly Pro Glu Leu Lys Lys Pro Gly Glu Thr Val Lys Ile Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asn Tyr Gly Met Asn Trp Val Lys Gln Thr Pro Gly Lys Gly Leu Lys Trp Met Gly Trp Ile Asn Thr Tyr Thr Gly Glu Pro Thr Tyr Ala Asp Asp Phe Lys Gly Arg Phe Ala Phe Ser Leu Glu Thr Ser Ala Ser Thr Ala Phe Leu Gln Ile Gln Gln Pro Gln Asn Met Arg Thr Met Ala Thr Tyr Phe Cys Val Arg Phe Ile Ser Lys Gly Asp Tyr Trp Gly Gln Gly Thr Ser Val Thr Val Ser Ser __________________________________________________________________________

28. The recombinant DNA compound of claim 27 wherein the coding strand is:

space="preserve" listing-type="tabular">__________________________________________________________________________ ATG GAT TGG CTG TGG AAC TTG CTA TTC CTG ATG GCA GCT GCC CAA AGT GCC CAA GCA CAG ATC CAG TTG GTG CAG TCT GGA CCT GAG CTG AAG AAG CCT GGA GAG ACA GTC AAG ATC TCC TGC AAG GCT TCT GGG TAT ACC TTC ACA AAC TAT GGA ATG AAC TGG GTG AAG CAG ACT CCA GGA AAG GGT TTA AAG TGG ATG GGC TGG ATA AAC ACC TAC ACT GGA GAA CCA ACA TAT GCT GAT GAC TTC AAG GGA CGG TTT GCC TTC TCT TTG GAA ACC TCT GCC AGC ACT GCC TTT TTG CAG ATT CAA CAA CCT CAG AAT ATG AGG ACT ATG GCT ACA TAT TTC TGT GTA AGA TTT ATT TCT AAG GGG GAC TAC TGG GGT CAA GGA ACG TCA GTC ACC GTC TCC TCA GCC AAA ACA ACA GCC CCA TCG GTC TAT CCA CTG GCC CCT GTG TGT __________________________________________________________________________

34. A recombinant DNA vector that comprises the DNA sequence of claim 27, wherein the first DNA sequence is derived from a murine hybridoma.

40. The recombinant DNA vector of claim 34, wherein the second DNA sequence is derived from a human source.

43. The recombinant DNA vector of claim 40, wherein the second DNA sequence encodes the constant region of human IgG1.

44. The recombinant DNA vector of claim 40, wherein the second DNA sequence encodes the constant region of human IgG2.

45. The recombinant DNA vector of claim 40, wherein the second DNA sequence encodes the constant region of human IgG3.

46. The recombinant DNA vector of claim 40, wherein the second DNA sequence encodes the constant region of human IgG4.

47. The recombinant DNA vector of claim 43 that is plasmid CH2A5.

48. The recombinant DNA vector of claim 44 that is plasmid CH2A5IG2.

49. The recombinant DNA vector of claim 45 that is plasmid CH2A5IG3.

50. The recombinant DNA vector of claim 46 that is plasmid CH2A5IG4.

53. A recombinant DNA expression vector of claim 40 that further comprises a promoter and translational activating sequence positioned to drive expression of said DNA.

56. The recombinant DNA expression vector of claim 53 wherein said promoter is the Adenovirus Late Promoter.

57. The recombinant DNA expression vector of claim 61 that is plasmid pL-HD.

58. The recombinant DNA expression vector of claim 56 wherein the second DNA sequence encodes the constant region of human IgG1.

59. The recombinant DNA expression vector of claim 56 wherein the second DNA sequence encodes the constant region of human IgG2.

60. The recombinant DNA expression vector of claim 56 wherein the second DNA sequence encodes the constant region of human IgG3.

61. The recombinant DNA expression vector of claim 56 wherein the second DNA sequence encodes the constant region of human IgG4.

62. The recombinant DNA expression vector of claim 58 that is plasmid pH1-HD.

63. The recombinant DNA expression vector of claim 59 that is plasmid pH2-HD.

64. The recombinant DNA expression vector of claim 60 that is plasmid pH3-HD.

65. The recombinant DNA expression vector of claim 61 that is plasmid pH4-HD.

66. A method for expressing recombinant and chimeric KS1/4 antibody chains in a recombinant non-lymphoid host cell, said method comprising:

(1) transforming said host cell with a recombinant DNA expression vector or vectors that comprise;

(a) a promoter and translational activating sequence that functions in said non- lymphoid host cell; and

(b) a DNA sequence that encodes a recombinant or chimeric KS1/4 antibody chain or chains, said DNA sequence being positioned for expression from said promoter and activating sequence; and

(2) culturing said host cell transformed in step (1) under conditions suitable for expression of recombinant or chimeric immunoglobulin chains.

67. The method of claim 66, wherein said recombinant host cell is selected from the group consisting of 293 cells and AV12 cells.

68. The method of claim 67, wherein said recombinant host cell in step 2 is AV12 cells.

69. The method of claim 68, wherein said recombinant host cell in step 2 is AV12/pL-HD.

70. The method of claim 68, wherein said recombinant host cell in step 2 is AV12/pH1-HD.

71. The method of claim 68, wherein said recombinant host cell is step 2 is AV12/pH2-HD.

72. The method of claim 68, wherein said recombinant host cell in step 2 is AV12/pH3-HD.

73. The method of claim 68, wherein said recombinant host cell in step 2 is AV12/pH4-HD.

74. The method of claim 68, wherein said recombinant host cell in step 2 is AV12/pL-HD/pH1-HD.

75. The method of claim 68, wherein said recombinant host cell in step 2 is AV12/pL-HD/pH2-HD.

76. The method of claim 68, wherein said recombinant host cell in step 2 is AV12/pL-HD/pH3-HD.

77. The method of claim 68, wherein said recombinant host cell in step 2 is AV12/pL-HD/pH4-HD.