Table 1 Comparison of three main T cell-based immunotherapies: ICI, CAR T cell, and BiTE

Structure

Monoclonal antibody targeting immune checkpoint proteins

A T cell from patients that are genetically re-engineered to present a synthetic transmembrane receptor on the surface to target a tumor antigen on tumor cells

A recombinant antibody comprised of two tandem scFv, one binding CD3 on T cells, the other targeting a tumor antigen on tumor cells

Anti-tumor mechanisms

Blocking the inhibitory immune checkpoint proteins that result in cytotoxic T cell-mediated immune response

Inducing tumor cell lysis by the formation of immune synapse between T cells and tumor cells

Inducing tumor cell lysis by the formation of immune synapse between T cells and tumor cells

Recruitment of T cells

Passive, acting on tumor-infiltrating and endogenous T cells to kill tumor cells

Active, redirecting engineered T cells outside of body to kill tumor cells

Passive, dependent on endogenous T cells and redirecting them to kill tumor cells

Production

Hybridoma technology, pervasive for all patients

Genetically engineering patient’s T cells outside of body, individualized for each patient

Genetically engineered and purified from mammalian cell lines, pervasive for all patients

Indications

Mainly in solid tumors with approval in a small part of hematologic neoplasms

All in hematologic neoplasms

All in hematologic neoplasms but with promising results for solid tumors

Toxicity

Immune-mediated AEs such as hyperactivation and hypersensitivity

On-target off-tumor effects, CRS, neurotoxicity

On-target off-tumor effects, CRS, neurotoxicity

Advantages

Broad-spectrum anti-tumor activity, easy production

MHC-independent, TCR-independent, endogenous T cell-independent

MHC-independent, TCR-independent, relatively easy production, tumor-infiltrating T cell-independent

Disadvantages

Tumor-infiltrating T cell-dependent, immune checkpoint expression-dependent, MHC-dependent, TCR-dependent

Lack of efficacy for solid tumors, long-term and complex production, antigen-dependent

Antigen-dependent, continuous administration due to a short half-life