Clinical feasibility and treatment outcomes with nonselected autologous tumor-infiltrating lymphocyte therapy in patients with advanced cutaneous melanoma.

Nonselected autologous tumor-infiltrating lymphocytes (TILs) may provide advantages over other treatments for solid tumors, including checkpoint inhibitor-refractory melanoma. This retrospective analysis reports a single-center experience of nonselected autologous TILs derived from digested tumors for compassionate use treatment of advanced cutaneous melanoma, including after programmed cell death protein 1 (PD-1) inhibition. Patients with histologically confirmed metastatic cutaneous melanoma and no standard-of-care treatment options underwent tumor resection for TIL product manufacturing.

Delivery of adoptive cell therapy in the context of the health-care system in the UK: challenges for clinical sites.

Advanced Therapy Medicinal Products (ATMPs) comprise novel cell, tissue and gene therapies and offer the potential of durable remissions for diseases where there is a high unmet clinical need. Once considered a niche area of academic research, ATMPs now represent one of the fastest-growing areas of clinical development. The field has seen a rapid expansion of academic and commercial entities successfully translating ATMP research into the clinic.

Tisotumab Vedotin in Previously Treated Recurrent or Metastatic Cervical Cancer.

Purpose: Tissue factor (TF) is a potential target in cervical cancer, as it is frequently highly expressed and associated with poor prognosis. Tisotumab vedotin, a first-in-class investigational antibody-drug conjugate targeting TF, has demonstrated encouraging activity in solid tumors. Here we report data from the cervical cancer cohort of innovaTV 201 phase I/II study (NCT02001623).

T-cell receptor and chimeric antigen receptor in solid cancers: current landscape, preclinical data and insight into future developments.

Purpose Of Review: The remarkable and durable clinical responses seen in certain solid tumours using checkpoint inhibitors and in haematological malignancies using chimeric antigen receptor (CAR) T therapy have led to great interest in the possibility of using engineered T-cell receptor (TCR) and CAR T therapies to treat solid tumours.

Recent Findings: In this article, we focus on the published clinical data for engineered TCR and CAR T therapy in solid tumours and recent preclinical work to explore how these therapies may develop and improve. We discuss recent approaches in target selection, encouraging epitope spreading and replicative capacity, CAR activation, T-cell trafficking, survival in the immunosuppressive microenvironment, universal T-cell therapies, manufacturing processes and managing toxicity.

The clinical efficacy of first-generation carcinoembryonic antigen (CEACAM5)-specific CAR T cells is limited by poor persistence and transient pre-conditioning-dependent respiratory toxicity.

The primary aim of this clinical trial was to determine the feasibility of delivering first-generation CAR T cell therapy to patients with advanced, CEACAM5 malignancy. Secondary aims were to assess clinical efficacy, immune effector function and optimal dose of CAR T cells. Three cohorts of patients received increasing doses of CEACAM5-specific CAR T cells after fludarabine pre-conditioning plus systemic IL2 support post T cell infusion.

Tremelimumab (anti-CTLA4) mediates immune responses mainly by direct activation of T effector cells rather than by affecting T regulatory cells.

Cytotoxic T Lymphocyte Antigen 4 (CTLA4) blockade has shown antitumor activity against common cancers. However, the exact mechanism of immune mediation by anti-CTLA4 remains to be elucidated. Further understanding of how CTLA4 blockade with tremelimumab mediates immune responses may allow a more effective selection of responsive patients.

Modulation of lymphocyte regulation for cancer therapy: a phase II trial of tremelimumab in advanced gastric and esophageal adenocarcinoma.

Purpose: Cytotoxic T lymphocyte antigen 4 (CTLA4), a key negative regulator of T-cell activation, is targeted by the antibody tremelimumab to release potentially useful antitumor activity.

Experimental Design: This phase II trial investigated tremelimumab as a second-line treatment for patients with metastatic gastric and esophageal adenocarcinomas. Tremelimumab was given every 3 months until symptomatic disease progression.

Adoptive transfer of T(reg) depleted autologous T cells in advanced renal cell carcinoma.

Purpose: CD4(+)CD25(+) regulatory T (T(reg)) cells are present in increased numbers in patients with advanced cancer and CD25(+) T cell depletion potentiates tumour immunity in animal models. The aim of this study was to assess the feasibility and safety of adoptive transfer of CD25(+) depleted autologous T cells in patients with advanced renal cell carcinoma and to examine resulting changes in lymphocyte subsets.

Patients And Methods: Six patients with advanced renal cell carcinoma underwent leukapheresis followed by conditioning chemotherapy with cyclophosphamide and fludarabine.

Anti-angiogenic therapy in the treatment of advanced renal cell cancer.

Metastatic renal cell cancer is associated with a poor prognosis and is resistant to traditional chemotherapy agents. The majority of tumours are associated with inactivation of the von Hippel-Lindau gene and subsequent overexpression of proangiogenic factors, including vascular endothelial growth factor (VEGF). Drugs targeting these pathways have undergone clinical testing in renal cell cancer with encouraging results.

Killing of non-Hodgkin lymphoma cells by autologous CD19 engineered T cells.

Adoptive immunotherapy with tumour-specific T cells is an emerging technology that may be applicable to a broad range of cancers. However, tumours can avoid T cell-mediated attack through multiple mechanisms including downregulation of major histocompatability complex (MHC). Consequently, engineering T cells to target intact protein antigen directly, thus bypassing the need for MHC presentation, can facilitate T cell targeting of tumour cells.