Switchable CAR-T Cells Outperformed Traditional Antibody-Redirected Therapeutics Targeting Breast Cancers

Area of Science:

• Immunotherapy
• Oncology
• Biotechnology

Background:

• Various antibody-redirected immunotherapies like ADCs, bsAbs, and CAR-T cells exist for cancer treatment.
• Her2-expressing breast cancers are a target for these therapies.
• Limitations in current approaches necessitate novel strategies.

Purpose of the Study:

• To develop and compare novel Her2-targeted immunotherapies for breast cancer.
• To evaluate the efficacy of switchable CAR-T (sCAR-T) cells against Her2-expressing breast cancers.
• To engineer bispecific sCAR-T cells to overcome antigen escape.

Main Methods:

• Generation of homogeneous Her2-targeted ADC, bsAb, and FITC-modified antibody using unnatural amino acids.
• Development of anti-FITC sCAR-T cells for Her2-targeting.
• Comparison of sCAR-T cell activity with ADC and bsAb approaches.
• Design and testing of bispecific sCAR-T cells targeting Her2 and IGF1R.

Main Results:

• sCAR-T cells exhibited comparable activity to conventional anti-Her2 CAR-T cells.
• sCAR-T cells demonstrated superior efficacy compared to ADC and bsAb approaches.
• Bispecific sCAR-T cells targeting Her2 and IGF1R showed enhanced activity against cancer cells with low Her2 expression.
• sCAR-T cells proved effective against Her2-expressing breast cancer cells.

Conclusions:

• sCAR-T cells represent a promising therapeutic option for breast cancer.
• This approach is particularly effective for patients with low or heterogeneous Her2 expression.
• The study enhances understanding of cancer therapeutics and the application of sCAR-T cells.