Driving CARs on the uneven road of antigen heterogeneity in solid tumors
N Chen, X Li, NK Chintala, ZE Tano… - Current opinion in …, 2018 - Elsevier
N Chen, X Li, NK Chintala, ZE Tano, PS Adusumilli
Current opinion in immunology, 2018•ElsevierHighlights•Solid tumor-specific antigen expression is a limitation for CAR T-cell
therapy.•Affinity of CARs can significantly influence T-cell effector function.•Novel CAR
design and targeting strategies can overcome above obstacles.Uniform and strong
expression of CD19, a cell surface antigen, on cells of B-cell lineage is unique to
hematologic malignancies. Tumor-associated antigen (TAA) targets in solid tumors exhibit
heterogeneity with regards to intensity and distribution, posing a challenge for chimeric …
therapy.•Affinity of CARs can significantly influence T-cell effector function.•Novel CAR
design and targeting strategies can overcome above obstacles.Uniform and strong
expression of CD19, a cell surface antigen, on cells of B-cell lineage is unique to
hematologic malignancies. Tumor-associated antigen (TAA) targets in solid tumors exhibit
heterogeneity with regards to intensity and distribution, posing a challenge for chimeric …
Highlights
- Solid tumor-specific antigen expression is a limitation for CAR T-cell therapy.
- Affinity of CARs can significantly influence T-cell effector function.
- Novel CAR design and targeting strategies can overcome above obstacles.
Uniform and strong expression of CD19, a cell surface antigen, on cells of B-cell lineage is unique to hematologic malignancies. Tumor-associated antigen (TAA) targets in solid tumors exhibit heterogeneity with regards to intensity and distribution, posing a challenge for chimeric antigen receptor (CAR) T-cell therapy. Novel CAR designs, such as dual TAA-targeted CARs, tandem CARs, and switchable CARs, in conjunction with inhibitory CARs, are being investigated as means to overcome antigen heterogeneity. In addition to heterogeneity in cancer-cell antigen expression, the key determinants for antitumor responses are CAR expression levels and affinity in T cells. Herein, we review CAR T-cell therapy clinical trials for patients with lung or pancreatic cancers, and provide detailed translational strategies to overcome antigen heterogeneity.
Elsevier