T cell receptor mimic antibodies for cancer therapy

Area of Science:

• Immunology
• Oncology
• Biotechnology

Background:

• Limited availability of tumor-specific surface protein epitopes hinders development of cancer-specific monoclonal antibodies (mAb) with low cross-reactivity to healthy cells.
• Mutated and overexpressed oncoproteins are often intracellular (cytoplasmic or nuclear), not readily accessible for antibody targeting.
• Cancer cells can present peptides derived from these intracellular proteins on their surface via human leukocyte antigen (HLA) molecules.

Approach:

• T cell receptor mimic (TCRm) monoclonal antibodies (mAb) are engineered to specifically recognize these peptide-HLA complexes on cancer cells.
• This approach enables the selective targeting of cancer cells by leveraging T cell receptor (TCR) mimicry.
• Review of the current state-of-the-art, challenges, and future opportunities in TCRm mAb development is presented.

Key Points:

• TCRm mAb offer a strategy to overcome the challenge of identifying unique cancer cell surface targets.
• Recognition of intracellular mutated or overexpressed proteins presented via HLA molecules allows for cancer cell specificity.
• Several TCRm mAb candidates are progressing towards clinical trials, indicating therapeutic potential.

Conclusions:

• TCRm mAb represent a promising avenue for developing highly specific cancer immunotherapies.
• The ability to target intracellular tumor antigens presented by HLA molecules expands the scope of antibody-based cancer treatments.
• Advancements in TCRm technology are paving the way for novel clinical applications in oncology.