Nanobody-based therapeutics against colorectal cancer: Precision therapies based on the personal mutanome profile and tumor neoantigens

Monoclonal antibodies and vaccines have widely been studied for the immunotherapy of cancer, while their large size appears to limit their functionality in solid tumors, in large part due to unique properties of tumor microenvironment such as high pressure of tumor interstitial fluid. To tackle such limitations, smaller formats of antibodies have been developed, including antigen-binding fragments, single-chain variable fragments, single variable domain of camelid antibody (so-called nanobody (Nb) or VHH). Of these, Nbs offer great immunotherapy potentials because of their advantageous physicochemical and pharmacological features, including small size, high stability, and excellent tissue penetration. Besides, the therapeutic impacts of Nbs can be improved by their modifications and functionalizations (e.g., PEGylation and conjugation to the Fc domain, peptide tags, drugs, toxins, aptamers, and radionuclides). This review aims to provide comprehensive insights into key signaling networks of colorectal cancer and discuss Nb-based precision immunotherapy of colorectal cancer.