Cancer treatment

The arsenal of weapons used to treat these insidious diseases is rapidly expanding.

Scientists are trying to work out how to balance potency with toxicity and tackle the cost of next-generation therapeutics.

Although natural-killer-cell therapies are safer than T-cell therapies and offer other advantages, they require upgrades to overcome their limited lifespan and susceptibility to immunosuppression.

Therapies that treat while diagnosing — theranostics — can extend length of survival and improve the quality of life for some people with advance-stage cancer.

Advances in in situ therapeutic cancer vaccines offer a mode of treatment that could redeem the promise of previous false dawns.

Pitting new treatments against old, ineffective agents is neither ethical nor economical.

Armed with the right data, advances in machine learning could help oncologists to home in quickly on the best treatment strategies for their patients.

Antibody–drug conjugates have emerged as a powerful tool to deliver highly targeted cancer therapies. Next-generation antibody-drug conjugate designs aim to push the envelope even further.

Brody and colleagues discuss the current status and potential of cancer vaccines, highlighting challenges and opportunities to advance promising candidates to the clinic.

In the final report of a phase 1/2 trial evaluating allogeneic CD19-specific CAR-NK cells armored with IL-15 in patients with CD19⁺ hematologic malignancies, the therapy was shown to be safe and efficacious with distinct cord blood features associated with response.

Here the authors review CAR T cell engineering and immunotherapy for cancer and juxtapose state-of-the-art developments with CAR NK cells as part of our Cancer Immunology series of Reviews.

This Review explores in detail the complexity of NK cell biology in humans and highlights the role of these cells in cancer immunity.

The probiotic Lactococcus lactis has been used for the delivery of therapeutic molecules. Here the authors engineer Lactococcus lactis to express a fusion protein of Flt3L and OX40 ligand, eliciting anti-tumor immune response in preclinical cancer models.

Antibody–drug conjugates (ADCs) are effective cancer drugs that have been approved for more than 20 specific indications. Nonetheless, acquired resistance and adverse events both limit the effectiveness of these agents. In this Review, the authors describe the development of novel ADC designs, including bispecific ADCs, probody–drug conjugates, immune-stimulating ADCs, protein-degrader ADCs and dual-drug ADCs. all of which have the potential to address these challenges and provide more effective ADCs.

Ideker and colleagues present NeST-VVN, a deep learning model based on cancer protein assembly data that can be used to predict the response and resistance of cancer cells to CDK4/6 inhibitors.

A deep residual learning framework identifies microsatellite instability in histology slides from patients with cancer and can be used to guide immunotherapy.

Theodorescu and colleagues describe a Molecular Twin approach that integrates multi-omic and computational pathology data from patients with pancreatic ductal adenocarcinoma using artificial intelligence to predict clinical outcomes.

A cancer vaccine is delivered to the lung by an engineered attenuated influenza virus.

Advances in technology have enabled the development of several novel antibody–drug conjugates (ADCs) with encouraging clinical activity in patients with advanced-stage solid tumours. Indications for these therapies are expanding rapidly to earlier lines of therapy. Nonetheless, the toxicities of these various agents are not trivial and can be fatal, even in patients with early stage disease. In this Review, the authors summarize the toxicities of ADCs in patients with solid tumours both as monotherapies and in combination with other agents and discuss various ongoing research efforts attempting to optimize the therapeutic index of these agents.