TARGETING CYTOTOXIC CELLS WITH CHIMERIC RECEPTORS FOR ADOPTIVE IMMUNOTHERAPY
First Claim
Patent Images
1. A purified, or non-naturally occurring, NK cell receptor chimeric antigen receptor (NKR-CAR) comprising one, two or all of:
- an extra-cellular antigen binding domain; and
a transmembrane domain; and
a cytoplasmic domain.
3 Assignments
0 Petitions
Accused Products
Abstract
The present invention provides compositions and methods for regulating the specificity and activity of T cells. In one embodiment, the invention provides a type of chimeric antigen receptor (CAR) wherein the CAR is termed a “KIR-CAR” which is a CAR design comprising a component of a receptor naturally found on natural killer (NK) cells. In one embodiment, the NK receptor includes but is not limited to a naturally occurring activating and inhibitory receptor of NK cells known as a killer cell immunoglobulin-like receptor (KIR).
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Citations
252 Claims
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1. A purified, or non-naturally occurring, NK cell receptor chimeric antigen receptor (NKR-CAR) comprising one, two or all of:
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an extra-cellular antigen binding domain; and a transmembrane domain; and a cytoplasmic domain. - View Dependent Claims (5, 6, 7, 9, 11)
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2-4. -4. (canceled)
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8. (canceled)
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10. (canceled)
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12-13. -13. (canceled)
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14. A purified, or non-naturally occurring, killer cell immunoglobulin-like receptor chimeric antigen receptor (KIR-CAR) comprising:
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an extra-cellular antigen binding domain; and a transmembrane domain or cytoplasmic domain. - View Dependent Claims (115, 149)
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15-66. -66. (canceled)
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67. A nucleic acid comprising:
(a) sequence that encodes a first killer cell immunoglobulin-like receptor chimeric antigen receptor (KIR-CAR), wherein the first KIR-CAR comprises an extra-cellular antigen binding domain; and
a transmembrane domain, or cytoplasmic domain.- View Dependent Claims (68, 69, 70, 72, 81, 82, 83, 84, 86, 87, 91, 92, 101, 104, 106, 144, 145, 148, 150)
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71. (canceled)
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73-80. -80. (canceled)
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85. (canceled)
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88-90. -90. (canceled)
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93-100. -100. (canceled)
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102-103. -103. (canceled)
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105. (canceled)
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107-114. -114. (canceled)
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116-143. -143. (canceled)
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146-147. -147. (canceled)
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151-167. -167. (canceled)
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168. A purified, or non-naturally occurring, natural cytotoxicity receptor chimeric antigen receptor (NCR-CAR) comprising:
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an extra-cellular antigen binding domain; a transmembrane domain; and a cytoplasmic domain.
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169-187. -187. (canceled)
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188. A purified, or non-naturally occurring, signaling lymphocyte activation molecule family chimeric antigen receptor (SLAMF-CAR) comprising:
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an extra-cellular antigen binding domain; a transmembrane domain; and a SLAMF cytoplasmic domain.
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189-197. -197. (canceled)
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198. A purified, or non-naturally occurring, Fc receptor chimeric antigen receptor (FcR-CAR) comprising:
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an extra-cellular antigen binding domain; a transmembrane domain a transmembrane domain comprising a positively charged moiety; and a CD16 or CD64 cytoplasmic domain.
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199-212. -212. (canceled)
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213. A purified, or non-naturally occurring, Ly49 receptor chimeric antigen receptor (Ly49-CAR) comprising:
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an extra-cellular antigen binding domain; and a transmembrane domain.
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214-232. -232. (canceled)
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233. A cytotoxic cell comprising:
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a first non-naturally occurring chimeric membrane embedded receptor comprising an antigen binding domain; and a second non-naturally occurring chimeric membrane embedded receptor comprising an antigen binding domain, wherein; (i) the antigen binding domain of one of said first and said second non-naturally occurring chimeric membrane embedded receptor does not comprise a light chain variable domain and a heavy chain variable domain; (ii) the antigen binding domain of one of said first and said second non-naturally occurring chimeric membrane embedded receptor comprises an scFv, and the other is other than an scFv; (iii) when present on the surface of a cell, the antigen binding domains of said first and said second non-naturally occurring chimeric membrane embedded receptor, associate with one another less than if both were scFv antigen binding domains; (iv) when present on the surface of a cell, binding of the antigen binding domain of said first non-naturally occurring chimeric membrane embedded receptor to its cognate antigen is not substantially reduced by the presence of said second non-naturally occurring chimeric membrane embedded receptor; (v) the antigen binding domain of one of said first and said second non-naturally occurring chimeric membrane embedded receptor, comprises a single VH domain; (vi) the antigen binding domain of one of said first and said second non-naturally occurring chimeric membrane embedded receptor, comprises an scFv, and the other comprises a single VH domain; (vii) the antigen binding domain of one of said first and said second non-naturally occurring chimeric membrane embedded receptor, comprises an scFv, and the other comprises a nanobody;
or(viii) the antigen binding domain of one of said first and said second non-naturally occurring chimeric membrane embedded receptor, comprises an scFv, and the other comprises a camelid VHH domain. - View Dependent Claims (237, 239, 249, 251)
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234-236. -236. (canceled)
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238. (canceled)
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240-247. -247. (canceled)
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248. A nucleic acid comprising a sequence that encodes a first and second non-naturally occurring chimeric membrane embedded receptor comprising an antigen binding domain,
wherein: -
(i) the antigen binding domain of one of said first and said second non-naturally occurring chimeric membrane embedded receptor does not comprise a light chain variable domain and a heavy chain variable domain; (ii) the antigen binding domain of one of said first and said second non-naturally occurring chimeric membrane embedded receptor comprises an scFv, and the other is other than an scFv; (iii) when present on the surface of a cell, the antigen binding domains of said first and said second non-naturally occurring chimeric membrane embedded receptor, associate with one another less than if both were scFv antigen binding domains; (iv) when present on the surface of a cell, binding of the antigen binding domain of said first non-naturally occurring chimeric membrane embedded receptor to its cognate antigen is not substantially reduced by the presence of said second non-naturally occurring chimeric membrane embedded receptor; (v) the antigen binding domain of one of said first and said second non-naturally occurring chimeric membrane embedded receptor, comprises a single VH domain; (vi) the antigen binding domain of one of said first and said second non-naturally occurring chimeric membrane embedded receptor, comprises an scFv, and the other comprises a single VH domain; (vii) the antigen binding domain of one of said first and said second non-naturally occurring chimeric membrane embedded receptor, comprises an scFv, and the other comprises a nanobody;
or(viii) the antigen binding domain of one of said first and said second non-naturally occurring chimeric membrane embedded receptor, comprises an scFv, and the other comprises a camelid VHH domain.
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250. (canceled)
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252-253. -253. (canceled)
Specification