Ablative immunotherapy
The invention disclosed herein relates generally to immunotherapy and, more specifically, to the use of immunotherapy for treating tumors and pathogen infected tissues by first priming patients with allogeneic cells designed to be rejected by a Th1 mediated mechanism, then inducing necrosis or apoptosis in a tumor or pathogen infected lesion by methods such as cryotherapy, irreversible electroporation, chemotherapy, radiation therapy, ultrasound therapy, ethanol chemoablation, microwave thermal ablation, radiofrequency energy or a combination thereof applied against at least a portion of the tumor or pathogen infected tissue, and then delivering one or more doses of allogeneic cells (e.g., Th1 cells) within or proximate to the tumor or pathogen-infected tissue in the primed patient. The present invention provides an immunotherapeutic strategy to develop de-novo systemic (adaptive) immunity to a tumor or pathogen.
1. A therapeutic composition for treating a tumor in a patient comprising:
tumor antigens wherein the tumor antigens are tumor tissue subjected to necrosis; and
allogeneic activated T-cells suspended in media suitable for injection to a patient, wherein the allogeneic T-cells serve as an adjuvant to create an immune response, whereby the antigen presenting cells in the patient uptake the antigens and subsequently mature in the patient to systemically stimulate anti-tumor immunity.
2. The composition of claim 1 further comprising a priming composition wherein the priming composition comprises allogeneic cells.
3. The composition of claim 1 wherein the tumor antigens are generated in vivo.
4. The composition of claim 1 wherein the tumor antigens are generated ex vivo.
5. The composition of claim 1 wherein the antigens comprise chaperone proteins.
6. The composition of claim 1 wherein the allogeneic cells are activated by cross-linking of CD3/CD28 on the T-cells.
7. The composition of claim 1 wherein the activated T-cells are producing Th1 cytokines.
8. The composition of claim 1 wherein the composition comprises between about 1×10 7 and about 3×10 7 cells.
9. A vaccine for a patient against a tumor comprising: antigenic material from the tumor wherein the antigenic material from the tumor is tumor tissue subjected to necrosis; and allogeneic activated T-cells suspended in media suitable for injection, wherein the allogeneic cells create a rejection response and stimulate a delayed-type hypersensitivity response in the patient to the allogeneic cells thereby acting as an adjuvant to the stimulation of systemic anti-tumor immunity in the patient.
10. The vaccine of claim 9 further comprising a priming composition wherein the priming composition comprises allogeneic cells.
11. The composition of claim 9 wherein the tumor antigens are generated in vivo.
12. The composition of claim 11 wherein the antigens are generated by necrosis of a lesion.
13. The composition of claim 9 wherein the tumor antigens are generated ex vivo.
14. The composition of claim 9 wherein the antigens comprise chaperone proteins.
15. The composition of claim 9 wherein the allogeneic cells are activated by cross-linking of CD3/CD28 on the T-cells.
16. The composition of claim 9 wherein the activated T-cells are producing Th1 cytokines.
17. The composition of claim 9 wherein the composition comprises between about 1×10 7 and about 3×10 7 cells.