Method of vaccinating using allogeneic 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 method of vaccinating a patient having cancerous cells or an infected tissue, the method comprising:
administering to the patient a priming composition comprising activated Th1 memory allogeneic cells and nanobeads coated with anti-CD3 and anti-CD28 monoclonal antibodies, the activated allogeneic Th1 memory cells to be rejected by the patient's immune system in a manner that induces anti-allogeneic Th1 immunity, wherein the activated allogeneic Th1 memory cells are activated by expansion with antibody coated paramagnetic beads, debeaded to remove the paramagnetic beads, harvested from cell culture, incubated with the nanobeads and washed to remove any unassociated nanobeads prior to administering to the patient;
permitting the patient's immune system to develop an anti-allogeneic Th1 immune memory prior to injecting an antigenic composition; and
injecting into the patient the antigenic composition, wherein the antigenic composition comprises an autologous lysate and the Th1 memory allogeneic cells, wherein the autologous lysate comprises antigens from the cancerous cells or the infected tissue, and wherein the Th1 memory allogeneic cells are the same as the Th1 memory allogeneic cells in the priming composition, thereby creating a rejection response, stimulating a delayed-type hypersensitivity response to the antigens and stimulating a systemic anti-tumor or anti-pathogen immunity in the patient.
2. The method of claim 1 wherein between about 1×10 8 and about 1×10 10 allogeneic cells are administered.
3. The method of claim 1 wherein the patient's immune system is permitted between about 7 days to about 14 days to form an anti-allogeneic Th1 immune memory.
4. The method of claim 1 wherein the autologous lysate comprises heat shock proteins.
5. The method of claim 1 wherein the harvested Th1 memory cells are incubated with the nanobeads for at least 4 to 18 hours prior to infusion.