Volume 15 Issue 1, January 2018

Women's health is more than reproductive health. Why does this phrase still need to be repeated? This commentary highlights the urgent need to encourage more women to lead, research, and educate to move beyond stereotypes and to ensure we push forward in improving the lives of women everywhere.

The development of therapeutic cancer vaccines has been pursued for many decades. Many vaccines can elicit immunity to tumour antigens, although their clinical efficacy remains modest. Recent results from two clinical trials highlight the potential of personalized vaccination strategies, made possible by high-throughput approaches to the identification of immunogenic tumour neoantigens. Thus, therapeutic cancer vaccines might soon move into the mainstream.

On 30^th August 2017, tisagenlecleucel became the first chimeric antigen receptor (CAR)-T-cell therapy to be approved by the FDA. This approval has important implications for health-care systems because the use of this promising treatment presents considerable logistical, toxicological, and financial challenges. Moreover, the high price tag of US$475,000 is questionable, considering the major role of US taxpayers in covering the development, delivery, and supportive-care costs of this treatment.

TP53, encoding the tumour-suppressor p53, is the most frequently mutated gene across all human cancers. Similar to other transcription factors, p53 has proved notoriously difficult to target therapeutically; to date, no p53-targeted therapies have entered the clinic. The diversity ofTP53 mutations, which can be categorized across a spectrum of different functional classes, is increasingly recognized as an additional challenge to developing p53-directed treatments. Herein, Kanaga Sabapathy and David Lane review this 'rainbow of p53 mutants', and discuss the implications for anticancer therapies targeting p53 or directed by TP53status.

Cell-based immunotherapies are showing great promise in the treatment of even the most treatment-refractory of haematological malignancies. Herein, Jennifer Brudno and James Kochenderfer review the results obtained to date with CAR-T-cell therapies for lymphoma. They also discuss what has been learned regarding the limitations of CAR-T-cell therapies and areas for improvement relating to toxicity management, the design of CAR-T-cell products, conditioning regimens, and combination therapies.

Chimeric antigen receptor (CAR)-T-cell therapies are showing great promise in the treatment of cancer, particularly B-cell malignancies, but are associated with characteristic, potentially fatal toxicities, principally cytokine-release syndrome, CAR-T-cell-related encephalopathy syndrome, and haemophagocytic lymphohistiocytosis/macrophage-activation syndrome. Herein, the CAR-T-cell-therapy-associated TOXicity (CARTOX) Working Group, comprising multidisciplinary investigators from various institutions with clinical experience in the use of a range of CAR-T-cell platforms, review these acute toxicities and provide monitoring, grading, and management recommendations.