This invention is a novel combinatorial therapy design for cancer treatment.
Though the number of approved cancer therapies has risen dramatically over the past decade, it has become apparent that the efficacy of a single treatment is limited. Combinatorial therapy has become increasingly important, especially in the field of immunotherapy, where engaging multiple responses from the immune system can have a multiplicative effect on the efficacy of therapy over that of any single treatment. However, it is difficult to determine which drugs, in combination, will provide potent treatments. This technology shows improvements in tumor control by the addition of multiple, orthogonal immunotherapy treatments.
The combination of tumor associated antigen antibody treatment, cytokine therapy, immune checkpoint blockade, and/or administration of a cancer vaccine has shown significant increase in the control and cure of established tumors in preclinical mouse models. Tumor associated antigen (TAA) antibody therapy is a highly developed treatment with several approved drugs, but rather ineffective as a monotherapy. Likewise, chemokines such as interleukin-2 (IL-2) are often effective in only a small fraction of patients and while cancer vaccines have been able to generate large numbers of tumor-antigen reactive cells, they are often functionally deficient as a result of negative immune regulation against self-antigens. A checkpoint blockade is often achieved by specific blocking antibodies to one of the proteins involved in negative immune stimulation. The inventors have shown that in C57BL/6 mice subcutaneously injected with the syngeneic, aggressive, and poorly immunogenic B16F10 cell line that antibody and IL2 in combination with checkpoint blockade and/or cancer vaccine was highly effective at tumor control.
Substantially improved efficacy over monotherapy treatments
- Able to reject tumor re-challenge in the absence of therapy
- Well tolerated, with no substantial toxicities observed