• CD3 Molecule: As a vital component of the T-cell receptor (TCR) complex, CD3 is responsible for transducing antigen recognition signals into the cell interior. The engagement and ligation of CD3 can directly induce T-cell activation.
•  CD8 Molecule: CD8 Binding of MHC-peptide complexes in cis or trans Regulates CD8+ T-cell Responses. The coreceptor CD8αβ can greatly promote activation of T cells by strengthening T-cell receptor (TCR) binding to cognate peptide-MHC complexes (pMHC) on antigen presenting cells and by bringing p56Lck to TCR/CD3. CD8 can also bind to pMHC on the T cell (in cis) and that this inhibits their activation. 
• T-Cell Engagement (TCE): CD3 redirection bispecific antibodies bind tumor associated antigens (TAA) on cancer cells and CD3 on recruited T cells to elicit cancer cell cytotoxicity independent of T cell receptor specificity. Cancer cell cytotoxicity occurs through perforin and granzyme B release resulting in apoptosis through caspase pathway induction. 
• CD3/CD8/TAA Antibody: To circumvent the unintended activation of regulatory T cells (Tregs), which are typically CD4+, the antibody is engineered with a preferential affinity for CD8+ cells. This selectivity enhances cytotoxic efficacy while simultaneously mitigating immunosuppressive effects.

TCE Therapy in Hematologic Cancers 

• T-cell engagers (TCEs), mainly represented by bispecific antibodies (BsAbs), have become one of the most important immunotherapy platforms in hematologic malignancies, particularly multiple myeloma (MM) and B-cell lymphomas. By simultaneously binding a tumor-associated antigen and CD3 on T cells, TCEs redirect and activate the patient's own T cells to recognize and kill tumor cells.
•  Among these agents, BCMA-targeting TCEs have shown remarkable clinical efficacy. BCMA-directed TCEs have become important treatment options for relapsed or refractory MM. In addition, BCMA-targeting therapies are being actively explored in autoimmune diseases, where depletion of pathogenic B cells and plasma cells may help restore immune tolerance and achieve durable disease control.

Strain specific CD3E expression analysis in homozygous B-hCD3EDG/hCD8/hBCMA mice by flow cytometry. Splenocytes and blood cells were collected from wild-type C57BL/6JNifdc mice and homozygous B-hCD3EDG/hCD8/hBCMA mice, and analyzed by flow cytometry with species-specific anti-mouse CD3ε antibody (Biolegend, 100210) and anti-human CD3ε antibody (Biolegend, 317344).

CD8 expression analysis in wild-type C57BL/6JNifdc mice and homozygous humanized B-hCD3EDG/hCD8/hBCMA mice by flow cytometry. Splenocytes were collected from wild-type C57BL/6JNifdc mice (+/+) and homozygous B-hCD3EDG/hCD8/hBCMA mice (H/H, H/H, H/H) (female, 6-week-old). Protein expression was analyzed with anti-mouse CD8 antibody (Biolegend, 100730) anti-human CD8a antibody (Biolegend, 300908) and anti-human CD8b antibody (BD, 742392) by flow cytometry.

CD8 expression analysis in wild-type C57BL/6JNifdc mice and homozygous humanized B-hCD3EDG/hCD8/hBCMA mice by flow cytometry. Splenocytes were collected from wild-type C57BL/6JNifdc mice (+/+) and homozygous B-hCD3EDG/hCD8/hBCMA mice (H/H, H/H, H/H) (female, 6-week-old). Protein expression was analyzed with anti-mouse CD8 antibody (Biolegend, 100730) anti-human CD8a antibody (Biolegend, 300908) and anti-human CD8b antibody (BD, 742392) by flow cytometry.

CD8 expression analysis in wild-type C57BL/6JNifdc mice and homozygous humanized B-hCD3EDG/hCD8/hBCMA mice by flow cytometry. Splenocytes were collected from wild-type C57BL/6JNifdc mice (+/+) and homozygous B-hCD3EDG/hCD8/hBCMA mice (H/H, H/H, H/H) (female, 6-week-old). Protein expression was analyzed with anti-mouse CD8 antibody (Biolegend, 100730) anti-human CD8a antibody (Biolegend, 300908) and anti-human CD8b antibody (BD, 742392) by flow cytometry.

Human BCMA expression analysis in splenocytes. Spleen cells were collected from wild-type C57BL/6JNifdc mice and homozygous B-hCD3EDG/hCD8/hBCMA mice (Female, n=3). Human BCMA expression on plasma cells was analyzed by flow cytometry using anti-human BCMA antibody (Biolegend, 357504). Mice were stimulated with LPS and treated with γ-secretase inhibitor to enhance membrane BCMA expression.