Understanding the interaction between the immune system and cancer to enhance patient outcomes
How can we use the body’s immune system to prevent and treat cancer?
Adoptive cellular therapy. Cancer vaccines. Oncolytic viral therapy. Immune response modifiers. These are several prominent examples of how Roswell Park’s Tumor Immunology and Immunotherapy Program is harnessing the power of the immune system as a novel weapon in the battle against cancer.
It is now clear that traditional cancer therapies, such as radiotherapy and chemotherapy, used to fight advanced or metastatic disease, are not enough to further prolong patient survival or enhance their quality of life. Therefore, newer therapeutic interventions are necessary to meet these critical clinical challenges. With a singular focus, the scientific and clinical research activities in Roswell Park’s Tumor Immunology and Immunotherapy Program have pursued a different path, one that involves developing safe and effective immune-directed therapies, known as immunotherapy. These therapies attack cancer in a very different way – by using a patient's own immune system as the drug of choice.
Our multidisciplinary team of scientists and clinicians are world-class experts in nearly every field of oncology, and work alongside experts in biostatistics and bioinformatics, flow and image cytometry, vector production, to name a few, so we can develop, test and analyze the efficacy of these novel immunotherapies.
The Tumor Immunology and Immunotherapy Program at Roswell Park seeks to understand and decipher the complex relationship between the immune system and malignancy and to translate this fundamental knowledge into the development of novel diagnostic, preventive, and treatment paradigms.
Our research focuses on three key areas:
Tumor-immune interactions within its microenvironment
Immune-mediated mechanisms of tumor regression
Immunotherapies for clinical cancer care and control
These themes are dynamic and interactive, continually evolving to translate basic science discoveries to clinical application.
Taking advantage of the close collaborations among our scientists, our program relies on the validation of results from in vitro systems to in vivo preclinical or animal models.
The information derived from these in vitro and in vivo studies is then utilized to develop novel immune-based strategies, which may be used alone or combined with other conventional or experimental agents, to address important clinical questions. In turn, the answers generated in the clinical setting raise new questions that necessitate a return to the laboratory for detailed preclinical follow-up and testing.
This bi-directional exchange of information between laboratory and clinical investigators provides the opportunity to apply basic science and the underlying molecular mechanisms to clinically relevant questions.
Spotlight: Ben Seon, PhD
Patients with an aggressive form of non-Hodgkin’s lymphoma now have a new treatment option — and it began with the work of Roswell Park cancer scientist Ben Seon, PhD.
During his tenure at Roswell Park, Dr. Seon discovered the importance of the CD79b molecule in cancer biology and developed a unique anti-CD79b targeting monoclonal antibody. Consequently, the impact of this discovery translated to clinical application with FDA-approval of polatuzumab vedotin (Polivy™) in 2019, a new immunotherapy plus chemotherapy regimen for patients with this type of lymphoma.
SurVaxM was discovered, developed, and clinically translated entirely at Roswell Park. Drs. Fenstermaker and Ciesielski and colleagues have developed therapeutic vaccines against survivin, a non-mutated protein that is overexpressed in glioblastoma multiforme (GBM) and multiple types of other aggressive cancers as a novel anti-cancer agent.
Termed SurVaxM, this vaccine is a first-in-class immunogen targeting survivin. The vaccine acts by inducing antitumor immune responses. A Phase II trial in newly diagnosed GBM has just been completed at several major cancer centers led by Roswell Park, including the Cleveland Clinic, Dana-Farber, Massachusetts General Hospital and Beth Israel Deaconess Medical Center.
Ongoing Phase 1 trials are enrolling patients to test the combination of SurVaxM and Revlimid in multiple myeloma, as well as neuroendocrine tumors. A new Phase 1/2 study opened in June of 2020 for recurrent GBM, combining SurVaxM with Keytruda.
These studies have led to the preparation stages of a large multicenter Phase 2b trial of SurVaxM which began in 2022.
Dr. Thanavala and colleagues have continued their efforts to understand immune dysfunction in patients with advanced hepatocellular carcinoma (HCC).
Their earlier work demonstrated that treatment of HCC patients with sorafenib (a tyrosine kinase inhibitor) reduced the extent of immune suppression caused by regulatory T cells (Tregs), which was associated with increased overall survival.
Her team has extended this work to a newer generation of a more potent kinase inhibitor, termed Tivozanib and evaluated its impact on Tregs, as part of a Phase Ib/II trial (NCT01835223).
More clinical trials
This P01, a major program project grant, includes five Phase I/II trials, which will test the impact of novel combination regimens on reshaping the tumor microenvironment (TME) to facilitate the infiltration of tumor-specific cytotoxic T lymphocytes, thus potentially improving patient outcome to immune checkpoint inhibitor therapy (i.e., PD-1 blockade).
This Phase IIA trial studies the combinatorial efficacy of celecoxib, recombinant interferon alpha-2b, and rintatolimod in treating patients with colorectal cancer that has spread to the liver.
Celecoxib is thought to inhibit the growth of tumor cells by blocking a key enzyme for cell growth, as well as the immune suppressive function of myeloid populations within the TME. Recombinant interferon alpha-2b is a protein that can improve the body's innate immune response and may also interfere with the growth of tumor cells. Rintatolimod also acts as an immune agonist, albeit differently, to stimulate the innate immune system.
Fungal Pathway Leads Roswell Park Researchers to New Treatment Target for Pancreatic Cancer
Roswell Park researchers discovered of a fungus-activated pathway that fuels the production of a molecule present in cancerous cells in the pancreas, opening a possible new treatment avenue for patients with this devastating disease.
Dr. Dey and colleagues are currently investigating whether the combination of an antifungal agent and immune checkpoint inhibitor can improve antitumor immune responses and outcomes in patients with Pancreatic ductal adenocarcinoma (PDAC).
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- Orr B, Mahdi H, Fang Y, Strange M, Uygun I, Rana M, Zhang L, Suarez Mora A, Pusateri A, Elishaev E, Kang C, Tseng G, Gooding W, Edwards RP, Kalinski P, Vlad AM. Phase I Trial Combining Chemokine-Targeting with Loco-Regional Chemoimmunotherapy for Recurrent, Platinum-Sensitive Ovarian Cancer Shows Induction of CXCR3 Ligands and Markers of Type 1 Immunity. Clin Cancer Res. 2022 Jan 19. doi: 10.1158/1078-0432.CCR-21-3659. Epub ahead of print. PMID: 35046055.
- He X, Zhou S, Huang WC, Seffouh A, Mabrouk MT, Morgan MT, Ortega J, Abrams SI, Lovell JF. A Potent Cancer Vaccine Adjuvant System for Particleization of Short, Synthetic CD8+ T Cell Epitopes. ACS Nano. 2021 MAR 23; 15(3):4357-4371. DOI: 10.1021/acsnano.0c07680. 2021 Feb 19. PubMed PMID: 33606514.
- Tzetzo SL, Abrams SI. Redirecting macrophage function to sustain their "defender" antitumor activity. Cancer Cell. 2021 MAR 13; . DOI: 10.1016/j.ccell.2021.03.002. 2021 Mar 13. PubMed PMID: 33798473.
- Zsiros E, Lynam S, Attwood KM, Wang C, Chilakapati S, Gomez EC, Liu S (GG), Akers S, Lele S (DT), Frederick PJ, Odunsi K. Efficacy and Safety of Pembrolizumab in Combination With Bevacizumab and Oral Metronomic Cyclophosphamide in the Treatment of Recurrent Ovarian Cancer: A Phase 2 Nonrandomized Clinical Trial. JAMA Oncol. 2021 JAN 01; 7(1):78-85. DOI: 10.1001/jamaoncol.2020.5945. PubMed PMID: 33211063; PMCID: PMC7677872.
- Dey P, Kimmelman AC, DePinho RA. Metabolic Codependencies in the Tumor Microenvironment. Cancer Discov. 2021 May;11(5):1067-1081. DOI: 10.1158/2159-8290.CD-20-1211. Epub 2021 Jan 27. PMID: 33504580; PMCID: PMC8102306.
- Gandhi S, Pandey MR, Attwood K, Ji W, Witkiewicz AK, Knudsen ES, Allen C, Tario JD, Wallace PK, Cedeno CD, Levis M, Stack S, Funchain P, Drabick JJ, Bucsek MJ, Puzanov I, Mohammadpour H, Repasky EA, Ernstoff MS. Phase I Clinical Trial of Combination Propranolol and Pembrolizumab in Locally Advanced and Metastatic Melanoma: Safety, Tolerability, and Preliminary Evidence of Antitumor Activity. Clin Cancer Res. 2021 Jan 1;27(1):87-95. doi: 10.1158/1078-0432.CCR-20-2381. Epub 2020 Oct 30. PMID: 33127652; PMCID: PMC7785669.
Education & training
In addition to our research and clinical trials, we are also committed to training the next generation of basic and clinical scientists, who will lead the fight against cancer.
Trainees in Roswell Park’s Tumor Immunology PhD track study closely with program members and participate in all phases of basic and translational research.
Spotlight: Division of Translational Immuno-Oncology
Roswell Park is one of the first institutions in the nation to establish a Division of Translational Immuno-Oncology with state-of-the-art facilities and research laboratories.
This combination of core facilities and partnerships with academic centers and industry offers us the unique capability to develop and implement the next generation of innovative cancer immunotherapies for our patients.