Compositions for allogeneic cell therapy
First Claim
1. A composition of T-cells coated with anti-CD3 and anti-CD28 mAbs wherein the anti-CD3 and anti-CD28 are cross-linked by biodegradable particles coated with an agent reactive against said mAbs, and wherein said activated T-cells are suspended in an infusion media suitable for intravenous infusion at a concentration of at least 107 cells per ml of the infusion media.
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Abstract
A method of manipulating allogeneic cells for use in allogeneic cell therapy protocols is described. The method provides a composition of highly activated allogeneic T-cells which are infused into immunocompetent cancer patients to elicit a novel anti-tumor immune mechanism called the “Mirror Effect”. In contrast to current allogeneic cell therapy protocols where T-cells in the graft mediate the beneficial graft vs. tumor (GVT) and detrimental graft vs. host (GVH) effects, the allogeneic cells of the present invention stimulate host T-cells to mediate the “mirror” of these effects. The mirror of the GVT effect is the host vs. tumor (HVT) effect. The “mirror” of the GVH effect is the host vs. graft (HVG) effect. The effectiveness and widespread application of the anti-tumor GVT effect is limited by the severe toxicity of the GVH effect. In the present invention, the anti-tumor HVT effect occurs in conjunction with a non-toxic HVG rejection effect. The highly activated allogeneic cells of the invention can be used to stimulate host immunity in a complete HLA mis-matched setting in patients that have not had a prior bone marrow transplant or received chemotherapy and/or radiation conditioning regimens.
45 Citations
22 Claims
- 1. A composition of T-cells coated with anti-CD3 and anti-CD28 mAbs wherein the anti-CD3 and anti-CD28 are cross-linked by biodegradable particles coated with an agent reactive against said mAbs, and wherein said activated T-cells are suspended in an infusion media suitable for intravenous infusion at a concentration of at least 107 cells per ml of the infusion media.
- 6. A composition comprising a treatment effective amount of a population of cells, of which at least a portion are T-cells, and whereby said T-cells are labeled with an activating effective amount of one or more monoclonal antibodies, or portions thereof, and suspended in an infusion media suitable for intravenous infusion at a concentration of at least 107 cells per ml of the infusion media.
- 13. A composition of allogeneic T-cells activated with anti-CD3 and anti-CD28 mAbs wherein the T-cells are cross-linked to biodegradable particles coated with an agent reactive against said mAbs for enhanced cytokine and surface molecule expression prior to infusion into a patient, wherein the T-cells are suspended in infusion media at a concentration of at least 107 cells or ml of the infusion media.
- 17. A composition comprising a treatment effective amount of a population of cells, of which at least a portion are T-cells, and whereby said T-cells are labeled with an activating effective amount of one or more monoclonal antibodies, or portions thereof, and a cross-linking effective amount of an agent reactive against said monoclonal antibodies, wherein the T-cells are activated for enhanced cytokine and surface molecule expression prior to infusion into a patient in an infusion media at a concentration of at least 107 cells per ml of the infusion media.
Specification