The immune (r)evolution in cancer
CHAPEL HILL, N.C.—Heat Biologics Inc., a clinical-stage biopharmaceutical company focused on the development of novel cancer immunotherapies, presented the results of its preclinical research study entitled “Comparative Combination Cancer Immunotherapy with Vaccination and TNFRSF Stimulation” at the Keystone Symposia on Molecular and Cellular Biology: Immune Evolution in Cancer (X2) held March 9-14 in Whistler, British Columbia.
Dr. Taylor H. Schreiber, vice president of research and development at Heat Biologics, explains that TNFRSF stands for “tumor necrosis factor receptor super family.” The comparative combination study presented at Keystone underscored the complementary activity of vaccination and direct T cell co-stimulation and suggests that combination immunotherapy may be an effective treatment strategy for anti-tumor immunity. The studies conducted by Schreiber, along with Dr. Neal Schilling, Dr. Vadim V. Deyev and Dr. Eckhard R. Podack, provide the first systematic comparison of antitumor vaccination with Heat’s ImPACT therapy-based heat shock protein gp96-Ig platform given alone or in combination with direct T cell co-stimulation via various forms of TNFRSF, including OX40, 4-1BB, GITR and TNFRSF25. The data from this study demonstrate that Heat’s ImPACT platform immunotherapy in combination with certain T-cell co-stimulators provides synergistic CD8+ T- cell activation, reduces tumor burden and increases overall survival as compared to either intervention as single agents.
Schreiber notes that gp96 is the 96 kilodalton fraction of tumor-cell lysate that has been shown to be protective against new tumor challenges by binding to and delivering antigens that produce animmune response. Heat’s proprietary Immune Pan Antigen Cytotoxic Therapy (ImPACT) transforms allogenic living cancer cells into powerful machines that continually secrete heat shock protein gp96, reportedly the most potent mammalian adjuvant ever described, along with its chaperoned antigens.
ImPACT reprograms live cancer cells from a single tumor source to continually secrete gp96, a chaperone protein found in all human cells. In turn, gp96 chaperones tumor antigens to T cells and is designed to activate a robust, pan-antigen T cell immune response and direct killer T cells to attack the patient’s cancer. Heat’s ImPACT technology holds promise for treating a wide variety of different cancers.
“These types of head-to-head comparisons are necessary to gauge the relative effectiveness of specific combination therapeutics because single-agent, single-investigator studies in disparate preclinical tumor models cannot be evaluated in relative terms. These data clearly show the potential synergies between ImPACT-based vaccines and T cell co-stimulatory antibodies,” Schreiber commented. “Heat’s research and development team intends to continue to expand on these data and collaborate with leading oncology clinicians to rationally combine Heat’s ImPACT-based immunotherapy with checkpoint inhibitors and other therapies to bring much-needed breakthrough treatment options to cancer patients.”
Heat has initiated an aggressive development program to target its ImPACT Therapy against a range of diseases and is entering Phase 2 clinical trials with its first ImPACT Therapy-based product, HS-110, a treatment for non-small cell lung cancer and has initiated a large Phase 1/2 trial of its HS-410 against bladder cancer in patients with early-stage bladder cancer. Additional indications are in preclinical development. ImPACT Therapy is currently being tested for use against HIV, HCV and malaria, and has demonstrated promising prophylactic potential in preclinical testing.
Jeff Wolf, Heat’s CEO, commented, “We look forward to applying these findings for design enhancements to our future clinical trials. The company plans to explore potential collaborations with biopharmaceutical companies with advanced checkpoint inhibitors and T cell co-stimulatory molecules. We are excited to be part of the next wave of innovative cancer treatments and to the future possibility of utilizing Heat’s powerful ImPACT-based immunotherapy to extend the utility of checkpoint inhibitors to a wide range of cancers and settings.”
Heat Biologics is focused on developing its novel, “off-the-shelf” ImPACT therapeutic vaccines to combat a wide range of cancers. ImPACT Therapy is designed to deliver live, genetically-modified, irradiated human cells which are reprogrammed to “pump out” a broad spectrum of cancer-associated antigens together with the potent immune adjuvant gp96 to educate and activate a cancer patient’s immune system to recognize and kill cancerous cells.