Expert opinion on biological therapyMay 5, 2018

Ways to improve T-cell therapy against solid tumors using engineered immune signals and other methods

Circadian Biology Weekly Brief ↗PubMed ↗DOI ↗

Updated Apr 1, 2026

Abstract

Tumor-specific T-cells could eliminate tumor cells with minimal long-term toxicity, but significant success in treating solid tumors remains limited.

Current T-cell therapies have shown notable success in leukemia and lymphoma but struggle with solid tumors.
Limited costimulatory and cytokine signaling in solid tumors may contribute to the challenges faced by T-cell therapies.
Engineering CAR-T therapies to enhance cytokine signaling is likely necessary for improving responses against solid tumors.
Concerns exist regarding the potential for unchecked proliferation and potency of engineered T-cells, highlighting the need for careful regulation.
Methods to safely deactivate these engineered cells at the tumor site are essential for ensuring patient safety.

Simplified

INTRODUCTION: Cancer therapy has been transformed by the demonstration that tumor-specific T-cells can eliminate tumor cells in a clinical setting with minimal long-term toxicity. However, significant success in the treatment of leukemia and lymphoma with T-cells using native receptors or redirected with chimeric antigen receptors (CARs) has not been recapitulated in the treatment of solid tumors. This lack of success is likely related to the paucity of costimulatory and cytokine signaling available in solid tumors, in addition to a range of inhibitory mechanisms.

AREAS COVERED: We summarize the latest developments in engineered T-cell immunotherapy, describe the limitations of these approaches in treating solid tumors, and finally highlight several strategies that may be useful in mediating solid tumor responses in the future, while also ensuring safety of engineered cells.

EXPERT OPINION: CAR-T therapies require further engineering to achieve their potential against solid tumors. Facilitating cytokine signaling in CAR T-cells appears to be essential in achieving better responses. However, the engineering of T-cells with potentially unchecked proliferation and potency raises the question of whether the simultaneous combination of enhancements will prove safe, necessitating continued advancements in regulating CAR-T activity at the tumor site and methods to safely switch off these engineered cells.

Full Text

Full text is available at the source.

View Full Text ↗

Funding

Competing interests

Declaration of Interest. T Shum has filed patents related to adoptive T-cell therapy from Celgene Corporation. RL Kruse has filed a patent on CAR T-cell technology from Celgene Corporation. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose

PubMed

Ways to improve T-cell therapy against solid tumors using engineered immune signals and other methods

Abstract

Full Text

Funding

Competing interests

You found one interesting study. We’ll send the next 7.

What Lands in Your Inbox Each Week:

Recent issues from the circadian biology brief

Abstract

Full Text

Funding

Competing interests

Related papers

You found one interesting study. We’ll send the next 7.

What Lands in Your Inbox Each Week:

Recent issues from the circadian biology brief