Nat Commun: CD318, TSPAN8 and CD66c are candidate targets for CAR-T cell therapy for pancreatic cancer

Pancreatic cancer is the fourth leading cause of cancer-related deaths in Western countries.
Currently, surgery is still the only way possible cure, and only about 20% of patients at diagnosis showed a stage of the disease can be surgically removed when.
Therefore, research on new treatment strategies is imminent.

A new potential treatment method is CAR (Chimeric Antigen Receptor)-T cell therapy, and it has shown unprecedented efficacy in the treatment of B-cell malignancies.
The therapy usually relies on pan-B cell antigens, such as CD19 or CD20, and cannot distinguish between healthy cells and tumor cells.
It will cause all B cells to be consumed, and so far is still one of the main problems of CAR-T cell therapy for solid tumors .

A major obstacle to effective cellular immunotherapy for pancreatic ductal carcinoma (PDAC) is the lack of suitable tumor-specific antigens.
In order to meet this challenge, the researchers aim to propose a systematic method for CAR-T target therapy.

Candidate CAR targets for PDAC

In this study, the researchers combined experiments such as flow cytometry screening, biological information expression analysis, and immunofluorescence.
The researchers identified CLA, CD66c, CD318, and TSPAN8 as four target candidates among 371 antigens, and produced 32 CARs specific to these molecules.

Evaluation of CAR-T cell function in the transplanted tumor model

Based on target cell lysis, T cell activation and cytokine release, the researchers evaluated the activity of CAR-T cells.
Among the CAR-T cells specific for CD66c, CD318, and TSPAN8, CD318 has shown the efficacy of stabilizing the disease to completely eradicating tumors, followed by TSPAN8, which is the most promising potential based on functionality and predicted safety Candidate targets.

All in all, this study revealed potential candidate targets for CAR-T cell-based PDAC immunotherapy, as well as functional CAR constructs for these molecules.