Description

Specific T cell responses to tumor associated antigens from melanoma patients undergoing immune checkpoint blockade therapy

Biao Liu¹, Zheng Yan¹, Aula Alami¹, Christine Kelley¹, Emilio Flano¹, Pamela Carroll¹, Wendy Broom¹, F. Stephen Hodi², Jessica B. Flechtner^1*

¹Genocea Biosciences, Cambridge MA; ²Department of Medical Oncology, Dana-Farber Cancer Institute, Boston MA

*Corresponding author

Successful treatment of melanoma patients with immune checkpoint blockade (ICB) therapy has reinforced the importance of T cells in anti-tumor efficacy. However, ICB therapy is effective in <50% of patients and is associated with substantial toxicity. ATLAS^TM is a platform in which putative antigens are expressed as individual clones that can be processed by any subject’s antigen presenting cells and presented to autologous CD4⁺ or CD8⁺ T cells for measurement of recall responses. An ATLAS library expressing 23 full-length melanoma tumor-associated antigens (TAAs) was constructed and used to interrogate recall CD4⁺ and CD8⁺ T cell responses from 26 melanoma patients after pembrolizumab treatment. ATLAS™ was able to detect patient-specific T cell responses in each subject suggesting that T cell responses to TAAs can be measured in multiple, HLA-diverse patients. Discrete patient, antigen and cytokine-specific response profiles emerged. Aggregation of these profiles across patient cohorts could lead to insights about tumor responses to ICB therapy, with implications for both patient stratification and identification of novel immunotherapies. While more subjects need to be screened to draw firm conclusions, preliminary results suggest that: fewer T cell responses are identified in patients who fail to respond to therapy (non-responders); the breadth of responses increases in patients that respond to ICB therapy (responders); for the CD8⁺ T cell subset, responders have more TAA antigens that induce IFN-ɣ secretion than non-responders; for the CD4⁺ T cell subset, responses are nearly undetectable in the non-responders, using any cytokine. Our data suggest that TAA panels using the ATLAS platform could provide information on a patient’s potential responsiveness to ICB therapy.