PANVAC ? Cancer Vaccine for the Prevention and Treatment of Colorectal Cancer
Posted Oct 27 2011 8:00pm
Description of Invention: Cancer immunotherapy is an approach where tumor associated antigens (TAAs), which are primarily expressed in human tumor cells, and not expressed or minimally expressed in normal tissues, are employed to generate a tumor-specific immune response. Specifically, these antigens serve as targets for the host immune system and elicit responses that results in tumor destruction. The initiation of an effective T-cell immune response to antigens requires two signals. The first one is antigen-specific via the peptide/ major histocompatibility complex and the second or “costimulatory” signal is required for cytokine production, proliferation, and other aspects of T-cell activation.
The PANVAC technology employs avirulent poxviruses to present a combination of tumor-associated antigens (TAAs) and costimulatory molecules to activate T-cells and break the immune systems tolerance towards cancer cells. This is performed using recombinant poxvirus DNA vectors that encode both T-cell costimulatory molecules and TAAs. The combination of the costimulatory molecules B7.1, ICAM–1 and LFA–3, is known as TRICOM. Recombinant poxviral vaccines (vaccinia (V) and fowlpox (F) containing TRICOM have been evaluated in prime (V)/boost (F) regimens in preclinical models and in several clinical trials in patients with metastatic colorectal cancer. Additionally, PANVAC has shown promising survival results in treating patients with metastatic colorectal cancer.
Furthermore, recombinant poxviral TRICOM based vaccines can also be employed for the prevention and/or therapy of colorectal cancer containing a range of other TAAs such as the T-box transcription factor Brachyury.
The technology is in clinical stage, supported by clinical results and numerous publications.
TRICOM, contained in pox vectors have been evaluated in prime (V)/boost (F) regimens in preclinical models and in several clinical trials in patients with metastatic colorectal cancer.
Phase I and Phase II clinical data are available (to qualified licensees) for poxvirus recombinants containing transgenes for TRICOM, CEA–TRICOM, and PANVAC. Further clinical studies are ongoing.
Given the relatively more advanced stage of development of this technology, fewer validation studies are required compared to other immunotherapy related technologies.
Development Status: PANVAC is a pox-vector-based cancer vaccine in clinical stage development with high potential for leading to a new therapeutic approach in the prevention and treatment of colorectalcancer. A combination of carcinoembryonic antigen (CEA) and pan-carcinoma antigen MUC–1, and TRICOM, PANVAC has been used with promising results in treating metastatic colorectal cancer.
In a recent multicenter phase II clinical trial reported at ASCO 2011, improved survival was observed among patients vaccinated with PANVAC following resection of colorectal cancer metastases; at a median follow up of forty (40) months, the survival rate of vaccinated patients clearly exceeding that of the unvaccinated contemporary control population. T-cell responses to CEA were also observed in vaccinated patients.
Inventors: Jeffrey Schlom (NCI) James W Hodge (NCI) Dennis L Panicali (NCI)
Refer to the Federal Register announcement noted above (under Description) for a complete listing of the patent estate.
Collaborative Research Opportunity: A CRADA partner for the further codevelopment of this technology specifically in colorectal cancer is currently being sought by the Laboratory of Tumor Immunology and Biology, Center for Cancer Research, NCI. The CRADA partner will (a) generate and characterize recombinant poxviruses expressing specific tumor-associated antigens, cytokines, and/or T-cell costimulatory factors, (b) analyze the recombinant poxviruses containing these genes with respect to appropriate expression of the encoded gene product(s), (c) supply adequate amounts of recombinant virus stocks for preclinical testing, (d) manufacture and test selected recombinant viruses for use in human clinical trials for colorectal cancer, (e) submit Drug Master Files detailing the development, manufacture, and testing of live recombinant vaccines to support the NCI-sponsored IND and/or company-sponsored IND, (f) supply adequate amounts of clinical grade recombinant poxvirus vaccines for clinical trials conducted at the NCI Center for Cancer Research (CCR), and (g) provide adequate amounts of vaccines for extramural clinical trials, if agreed upon by the parties, and conduct clinical trials under company-sponsored or NCI-sponsored INDs. NCI will (a) provide genes of tumor-associated antigens, cytokines and other immunostimulatory molecules for incorporation into poxvirus vectors, (b) evaluate recombinant vectors in preclinical models alone and in combination therapies, and (c) conduct clinical trials for colorectal cancer of recombinant vaccines alone and in combination therapies.
Contact Michael Pollack at 301-435-3118 or email email@example.com for additional information about this CRADA opportunity.