Vaccine comprising allogeneic T-cells
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 pathogen in a patient comprising:
pathogen antigens wherein the pathogen antigens are pathogen infected tissue subjected to necrosis and wherein the pathogen antigens comprise chaperone proteins; and
allogeneic activated T-cells associated with nanobeads suspended in media suitable for injection to the 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-pathogen immunity, wherein the allogeneic cells are CD4+Th1 cells producing in excess of 2000 ng/ml/10 6 cells/6 hours of IFN-γ, wherein the CD4+Th1 cells were produced by normal donor T-cells expanded by CD3/CD28 T-cell expander beads, harvested after expansion, debeaded, and the debeaded cells incubated for about 4 to about 18 hours with nanobeads conjugated to antibodies that bind to CD3 and CD28 cell surface moieties for cross-linking of CD3/CD28 on the T-cells prior to infusion.
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 pathogen antigens are generated in vivo.
4. The composition of claim 1 wherein the pathogen antigens are generated ex vivo.
5. The composition of claim 1 wherein the activated T-cells are producing Th1 cytokines.
6. The composition of claim 1 wherein the composition comprises between about 1×10 7 and about 3×10 7 cells.
7. The composition of claim 1 wherein the activated T-cells are not pathogen specific T-cells.
8. A vaccine for a patient against a pathogen comprising:
antigenic material from tissue infected by the
pathogen, wherein the antigenic material comprises chaperone proteins; and allogeneic activated T-cells associated with nanobeads 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-pathogen immunity in the patient, wherein the antigenic material is generated by necrosis of a lesion and wherein the allogeneic cells are CD4+Th1 cells producing in excess of 2000 ng/ml/10 6 cells/6 hours of IFN-γ, wherein the CD4+Th1 cells were produced by normal donor T-cells expanded by CD3/CD28 T-cell expander beads, harvested after expansion, debeaded after expansion, and the debeaded cells incubated for about 4 to about 18 hours with nanobeads conjugated to antibodies that bind to CD3 and CD28 cell surface moieties for cross-linking of CD3/CD28 on the T-cells prior to infusion.
9. The vaccine of claim 8 further comprising a priming composition wherein the priming composition comprises allogeneic cells.
10. The vaccine of claim 8 wherein the pathogen antigens are generated in vivo.
11. The vaccine of claim 8 wherein the pathogen antigens are generated ex vivo.
12. The vaccine of claim 8 wherein the activated T-cells are producing Th1 cytokines.
13. The vaccine of claim 8 wherein the vaccine comprises between about 1×10 7 and about 3×10 7 cells.
14. The vaccine of claim 8 wherein the activated T-cells are not pathogen specific T-cells.