Allogeneic T-cell compositions for induction of IL-12
The present invention relates to compositions and methods that promote the induction of IL-12 in a patient. The composition includes activated allogeneic cells that are administered to a patient with a disease such as cancer. Administration of the composition skews the patient's immune response to a Th1 environment and produces detectable levels of IL-12 in the patient's plasma, without any IL-12 related toxicity.
1. A composition comprising between one and six intradermal doses, between one and two intratumoral doses and between five and ten intravenous doses of activated allogeneic Th1 cells with cross-linking agents that cross-link CD3 and CD28 cell surface moieties, wherein the intradermal doses comprise between 1×10 6 to 1×10 7 cells/ml, the intratumoral doses comprise between 1×10 7 to 1×10 8 cells/ml and the intravenous doses comprise between 1×10 7 to 1×10 9 cells/ml, respectively, wherein the cross-linking agents are immobilized on surface of biodegradable beads and wherein the Th1 cells, the cross-linking agents and the biodegradable beads are suspended in a non-nutrient media.
2. The composition of claim 1 , wherein the composition comprises between three and six intradermal doses, between one and two intratumoral doses and between six and nine intravenous doses, respectively.
3. The composition of claim 1 where the activated Th1 cells secrete one or more of the following Th1 cytokines: IL-2, IFN-gamma and GM-CSF.
4. The composition of claim 3 where the activated Th1 cells express DC maturation molecule CD40L and/or FasL on their surface.
5. The composition of claim 1 where the doses of Th1 cells are packaged in a syringe.
6. The composition of claim 1 wherein the cross-linking of CD3 and CD28 is through anti-CD3 and anti-CD28 monoclonal antibodies.