Trial Watch: Adoptively transferred cells for anticancer immunotherapy

Abstract

Immunotherapies aimed at strengthening immune effector responses against malignant cells are growing at exponential rates. Alongside, the impressive benefits obtained by patients with advanced melanoma who received adoptively transferred tumor-infiltrating lymphocytes (TILs) have encouraged the scientific community to pursue adoptive cell transfer (ACT)-based immunotherapy. ACT involves autologous or allogenic effector lymphocytes that are generally obtained from the peripheral blood or resected tumors, expanded and activated , and administered to lymphodepleted patients. ACT may be optionally associated with chemo- and/or immunotherapeutics, with the overall aim of enhancing the proliferation, persistence and functionality of infused cells, as well as to ensure their evolution in an immunological permissive local and systemic microenvironment. In addition, isolated lymphocytes can be genetically engineered to endow them with the ability to target a specific tumor-associated antigen (TAA), to increase their lifespan, and/or to reduce their potential toxicity. The infusion of chimeric antigen receptor (CAR)-expressing cytotoxic T lymphocytes redirected against CD19 has shown promising clinical efficacy in patients with B-cell malignancies. Accordingly, the US Food and Drug Administration (FDA) has recently granted 'breakthrough therapy' designation to a CAR-based T-cell therapy (CTL019) for patients with B-cell malignancies. Considerable efforts are now being devoted to the development of efficient ACT-based immunotherapies for non-hematological neoplasms. In this Trial Watch, we summarize recent clinical advances on the use of ACT for oncological indications.

A synergistic triad of chemotherapy, immune checkpoint inhibitors, and caloric restriction mimetics eradicates tumors in mice

“…adoptive T cell therapies, cancer vaccines). [53][54][55][56][57][58][59] Notwithstanding the aforementioned limitations, our results delineate a strategy for tumor treatment that involves a therapy consisting in the administration of three drug classes: (i) ICD inducers exemplified by MTX and OXA, (ii) CRMs exemplified by HC and Spd and substitutable for fasting (if the nutritional status of the patient allows it) and (iii) ICIs targeting the PD-1/PD-L1 interaction. As shown here, such a triple combination has the potential to cure the majority of mice bearing established fibrosarcomas.…”

Metabolic Regulation of CAR T Cell Function by the Hypoxic Microenvironment in Solid Tumors

“…To date, various trials using TILs for the treatment of melanoma as well as other solid tumors have been, and are being, conducted. The latest Trial Watch for cancer immunotherapy provides an overview of current trials [56]. TIL therapy for the treatment of metastatic melanoma is the most effective with durable, complete response rates >20% [57].…”

Trial watch: Peptide-based vaccines in anticancer therapy

“…132 Considerable attention in this sense has been attracted by immune checkpoint blockers, 86,133-136 despite initial setbacks linked to the lack of added therapeutic value when ipilimumab (an FDA-approved mAb targeting CTLA) was combined with a peptide vaccine targeting premelanosome protein (PMEL, also known as gp100) in melanoma patients. 137 Along the lines of previous Trial Watches from our series, 138,139 here we summarize recent clinical advances in the development of peptide-based therapeutic vaccines for cancer therapy.…”