Ablative Immunotherapy
The disclosure herein relates generally to immunotherapy and, more specifically, to the use of immunotherapy for treating tumors and pathogen infected tissues. The immunotherapy relates to first priming patients with allogeneic cells designed to be rejected by a Th1 mediated mechanism, then inducing in situ necrosis or apoptosis in a tumor or pathogen infected lesion. Necrosis or apoptosis can be induced 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. One or more doses of allogeneic cells (e.g., Th1 cells) are then delivered 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 or pathogen in a patient comprising:
allogeneic cells; and
antigens comprising the product of tumor necrosis or pathogen infected tissue necrosis, wherein the antigens are generated in situ, whereby the allogeneic cells and the in situ generated antigens elicit an immune response by the patient to create an anti-tumor or anti-pathogen 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 antigens are generated in situ by ablation of the tumor or pathogen infected tissue.
4 . The composition of claim 3 wherein the ablation is by cryoablation.
5 . The composition of claim 3 wherein the ablation is by electroporation.
6 . The composition of claim 1 wherein the antigens comprise tumor or pathogen antigens, heat shock proteins and combinations thereof.
7 . The composition of claim 1 wherein the allogeneic cells are activated T-cells.
8 . The composition of claim 1 wherein the allogeneic cells express high levels of Type 1 cytokines.
9 . The composition of claim 1 wherein the allogeneic cells express a high density of CD40L, TRAIL, FasL and combinations thereof on the cell surface.
10 . A vaccine composition comprising:
an adjuvant comprising allogeneic cells; and
antigens generated in situ by necrosis of diseased cells or tissue, wherein the presence of the adjuvant at the necrotic site along with the in situ generated antigens elicit an immune response by the patient to create immunity against the disease.
11 . The vaccine of claim 10 further comprising a priming composition wherein the priming composition comprises allogeneic cells.
12 . The vaccine of claim 10 wherein the antigens are generated in situ by ablation of the tumor or pathogen infected tissue.
13 . The vaccine of claim 12 wherein the ablation is by cryoablation.
14 . The vaccine of claim 12 wherein the ablation is by electroporation.
15 . The vaccine of claim 10 wherein the antigens comprise tumor or pathogen antigens, heat shock proteins and combinations thereof.
16 . The vaccine of claim 10 wherein the allogeneic cells are activated T-cells.
17 . The composition of claim 10 wherein the allogeneic cells express high levels of Type 1 cytokines
18 . The composition of claim 10 wherein the allogeneic cells express a high density of CD40L, TRAIL, FasL and combinations thereof on the cell surface.