Description of Research Expertise:
Human Cancer Immunology is the focus of our laboratory and clinical efforts.
The development of a systematic approach to identify and validate cancer neoantigens is a primary interest of our research laboratory. In collaboration with experts in cancer genomics, we have created a bioinformatics pipeline to identify tumor-specific missense mutations which encode neoantigenic peptides. Our team has successfully applied this strategy to develop the first test of personalized cancer vaccination in humans with melanoma. Ongoing proof-of-concept trials aim to test neoantigens as targets for various immunotherapy strategies in melanoma and other solid tumors. In particular, our work aims to characterize the functional and phenotypic landscape of vaccine-elicited T cells using molecular technologies.
A related interest is the development of cellular therapies for cancer. We are currently exploring the development of neoantigen-specific T cell therapy for use in patients. We work collaboratively with research groups in order to find novel solutions to overcome the inherent obstacles created by the tumor microenvironment. The long term goal is to advance and test personalized medicine based approaches in cancer patients. For more information, please see the Center for Cellular Immunotherapies home page.
Linette GP, Carreno BM.: Neoantigen Vaccines Pass the Immunogenicity Test Trends Mol Med. : 2017.
Larkin J, Minor D, D'Angelo S, Neyns B, Smylie M, Miller WH Jr, Gutzmer R, Linette G, Chmielowski B, Lao CD, Lorigan P, Grossmann K, Hassel JC, Sznol M, Daud A, Sosman J, Khushalani N, Schadendorf D, Hoeller C, Walker D, Kong G, Horak C, Weber J.: Overall Survival in Patients With Advanced Melanoma Who Received Nivolumab Versus Investigator's Choice Chemotherapy in CheckMate 037: A Randomized, Controlled, Open-Label Phase III Trial. J Clin Oncol. : 2017.
Zenga J, Nussenbaum B, Cornelius LA, Linette GP, Desai SC.: Management Controversies in Head and Neck Melanoma: A Systematic Review. JAMA Facial Plast Surg 19 (1): 53-62,2017.
Hodi FS1, Chesney J, Pavlick AC, Robert C, Grossmann KF, McDermott DF, Linette GP, Meyer N, Giguere JK, Agarwala SS, Shaheen M, Ernstoff MS, Minor DR, Salama AK, Taylor MH, Ott PA, Horak C, Gagnier P, Jiang J, Wolchok JD, Postow MA.: Combined nivolumab and ipilimumab versus ipilimumab alone in patients with advanced melanoma: 2-year overall survival outcomes in a multicentre, randomised, controlled, phase 2 trial. Lancet Oncol 17 (11): 1558-1568,2016.
Kaufman HL, Russell J, Hamid O, Bhatia S, Terheyden P, D'Angelo SP, Shih KC, Lebbé C, Linette GP, Milella M, Brownell I, Lewis KD, Lorch JH, Chin K, Mahnke L, von Heydebreck A, Cuillerot JM, Nghiem P.: Avelumab in patients with chemotherapy-refractory metastatic Merkel cell carcinoma: a multicentre, single-group, open-label, phase 2 trial. Lancet Oncol 17 (10): 1374-1385,2016.
Hundal J, Carreno BM, Petti AA, Linette GP, Griffith OL, Mardis ER, Griffith M: pVAC-Seq: A genome-guided in silico approach to identifying tumor neoantigens Genome Med 8 (1): 11-19,2016.
Postow MA, Chesney J, Pavlick AC, Robert C, Grossmann K, McDermott D, Linette GP, Meyer N, Giguere JK, Agarwala SS, Shaheen M, Ernstoff MS, Minor D, Salama AK, Taylor M, Ott PA, Rollin LM, Horak C, Gagnier P, Wolchok JD, Hodi FS.: Nivolumab and ipilimumab versus ipilimumab in untreated melanoma. N Engl J Med 372 (21): 2006-17,2015.
Carreno BM, Magrini V, Becker-Hapak M, Kaabinejadian S, Hundal J, Petti AA, Ly A, Lie WR, Hildebrand WH, Mardis ER, Linette GP.: A dendritic cell vaccine increases the breadth and diversity of melanoma neoantigen-specific T cells. Science 348 (6236): 803-8,2015.
Ding L, Kim M, Dees ND, Kanchi KL, Lu C, Griffith M, Fenstermacher D, Sung H, Miller CA, Goetz B, Wendl MC, Griffith O, Cornelius LA, Linette GP, Sondak VK, Fields RC, Ley TJ, Mulé JJ, Wilson RK, Weber JS.: Clonal Architecture and Driver Mutations in Metastatic Melanoma. PLOS One. 9 (11): 9e111153,2014.
Carreno BM, Becker-Hapak M, Huang A, Chan M, Alyasiry A, Lie WR, Aft RL, Cornelius LA, Trinkaus KM, Linette GP.: IL-12p70 producing patient DC vaccine elicits Tc1-polarized immunity. Journal of Clinical Investigation 123 (8): 3383-94,2013.