Personalized Cancer Vaccines
New therapies that exploit a patient’s immune system to seek and destroy tumors are revolutionizing the way we think about and treat cancer. Immune checkpoint therapies, for instance, which broadly activate T cells to attack cancer, have demonstrated remarkable and durable activity in some patients, however, we believe too many patients receiving these treatments experience no clinical benefit or see their cancer return.
The profound benefit and sometimes extreme toxicity that accompanies the broad T cell activation seen with immune checkpoint therapies has taught us that the critical next step in immune-mediated cancer treatment is leveraging innovative technology to direct T cells to specific, impactful targets at the site of the tumor.
Genocea’s proprietary ATLAS technology uses a cellular assay to comprehensively re-create a patient’s actual immune response to cancer. This means ATLAS identifies – not just predicts - antigens to which patients are responding, and can distinguish between those that stimulate productive T cell responses (CD4+ and CD8+ T cells) and those that are irrelevant or may actually inhibit response. With this information, we can uniquely discern the clinically meaningful T cell antigen targets that may identify which patients will benefit from treatment with cancer immunotherapies and drive the development of more effective cancer vaccines and immunotherapies.
GEN-009 – Personalized Neoantigen Cancer Vaccine Program
Genocea’s lead program, GEN-009, focuses on the development of personalized cancer vaccines by leveraging ATLAS to identify patient neoantigens, or newly formed antigens that are often found in tumor cells that have not been previously recognized by the immune system. These cancer vaccines are being designed to educate T cells to recognize and attack specific targets and thereby kill cancers.
Genocea plans to initiate a Phase 1 clinical trial for GEN-009 in a range of tumor types in the first half of 2018, and expects to report initial immunogenicity data in the first half of 2019.
World Class Partnerships Driving Novel Cancer Vaccine Development
- Checkmate Pharmaceuticals
Genocea and Checkmate are employing ATLAS to profile the T cell responses of approximately 20 patients enrolled in Checkmate’s ongoing Phase 1b clinical trial in metastatic melanoma. The T cell response signatures of those patients who respond to CMP-001 / pembrolizumab combination therapy will be compared to the signatures of those who do not respond, thereby potentially identifying antigens associated with positive or negative patient outcomes.
- Memorial Sloan Kettering Cancer Center
Genocea has partnered with researchers at Memorial Sloan Kettering Cancer Center to identify the complete repertoire of neoantigens found in patient tumors. Through this collaboration, ATLAS has discovered several neoantigens as biologically relevant T cell targets associated with significant cytotoxic T cell responses. Importantly, many of these neoantigens were not identified by commonly used predictive computer algorithms, and the majority of neoantigens that were identified by those algorithms were not associated with meaningful T cell responses in ATLAS. Additionally, multiple neoantigens were identified by ATLAS that were associated with a downregulation of immune response.
- Dana-Farber Cancer Institute
ATLAS’s advanced technology is also being leveraged to help identify patients that are most likely to respond, and very importantly, not respond, to immune checkpoint therapies. Due to the limited effectiveness of immune checkpoint therapy in most patients and the potential for significant adverse effects, it is imperative to identify the patients that will respond to these therapies. Results have demonstrated that patients that respond to immune checkpoint blockade therapy have a greater breadth of T cell activation than patients that do not respond to treatment. We are applying these results and expanding the utility of ATLAS as a prognostic tool to identify patients that could benefit from checkpoint inhibitor therapy.
- US Oncology Research
Genocea has entered an agreement with US Oncology Research that should allow Genocea to build substantial preclinical data to support personalized cancer vaccine clinical trials. US Oncology Research is the largest network of community oncologists in the US, and, through collaboration and shared purpose, provides the clinical, research, technology and business resources to ensure the growth and vitality of their independent, community-based oncology practices.
Epstein-Barr Virus is a human herpesvirus that infects about 95% of the population. While infection most commonly occurs in young children and without noticeable disease, acquisition of the virus later in life can lead to infectious mononucleosis. Symptoms may affect people for several months and are mainly caused by an exacerbated immune reaction to infected cells.
More recently, the virus has been associated with several types of cancer, notably Burkitt’s and Hodgkin lymphomas, gastric and nasopharyngeal carcinoma, and post-transplant lymphoproliferative disease. In fact, 1% of all cancers worldwide are associated with Epstein-Barr Virus. Thus, understanding and exploiting the immune responses to the virus provides a unique opportunity to create novel vaccine candidates that could impact both infectious disease and cancer.
Genocea has demonstrated the feasibility of utilizing the ATLAS platform to characterize the T cell responses to Epstein-Barr Virus in a pilot screening campaign and we are actively analyzing the T cell responses in more individuals.
Check out our presented work on Cancer Vaccines.