Abstract 1053P
Background
Adoptive cell therapy is a therapeutic strategy that may reverse dysfunction in endogenous TIL, through a process that involves emigration of T cells out of the immunosuppressive TME, significantly expanding the TIL ex vivo while reinvigorating them, and re-infusing the cells into the patient. To determine whether TIL generated using Iovance’s Gen 2 expansion protocol (D22 TIL) resulted in a reinvigorated TIL population, relative to endogenous TIL (D0), D0 and D22 TIL were assessed for phenotype, function and tumor reactivity.
Methods
Endogenous CD3+ TIL (D0), isolated from digested tumor biopsies, were sorted using FACS and compared to TIL expanded for 22 days using Iovance’s Gen 2 process (D22). T cell subsets from 7 paired D0 and D22 TIL from melanoma, cervical cancer, and head and neck squamous cell carcinoma were assessed for phenotypic and regulatory markers by FACS, function by in vitro activation, and tumor reactivity by autologous tumor co-culture.
Results
At D22 terminally differentiated T cells remained below D0 levels. D22 TIL upregulated markers associated with activation. Treg were mostly absent from D22 TIL. Furthermore, at D22, the CD8:CD4 ratio increased relative to D0, indicating preferential proliferation of CD8+ cells during. The main effector memory T cell (TEM) subset was enriched, suggesting a stem cell memory and central memory to TEM transition. The canonical exhaustion marker PD-1 decreased significantly at D22. Expansion of sorted PD-1+ cells suggested downregulated expression rather than T cell elimination. In all sample pairs, TCR induction of IFNg was dramatically enhanced at D22 vs D0. Finally, D22 TIL displayed greater specific in vitro tumor cytotoxicity than endogenous TIL.
Conclusions
Our results suggest that the ex vivo expansion of TIL, using Iovance’s Generation 2 process, reverses the dysfunctional state of the T cells from the tumor microenvironment, by transitioning their phenotypic, functional and tumor-reactive profile, thereby rendering the cells reinvigorated and capable of producing a potent and effective anti-tumor response in vivo.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Iovance Biotherapeutics, Inc.
Funding
Iovance Biotherapeutics, Inc.
Disclosure
M.R. Simpson-Abelson, C. Chartier: Travel/Accommodation/Expenses, Shareholder/Stockholder/Stock options, Full/Part-time employment: Iovance Biotherapeutics. K. D’Arigo: Shareholder/Stockholder/Stock options, Full/Part-time employment: Iovance Biotherapeutics, Inc. F. Hilton: Full/Part-time employment: Iovance Biotherapeutics, Inc. M. Fardis: Speaker Bureau/Expert testimony, Leadership role, Travel/Accommodation/Expenses, Shareholder/Stockholder/Stock options, Licensing/Royalties, Full/Part-time employment, Officer/Board of Directors: Iovance Biotherapeutics, Inc.; Shareholder/Stockholder/Stock options: Gilead; Shareholder/Stockholder/Stock options: AbbVie; Officer/Board of Directors: Kartos Therapeutics.