Trifunctional Triomab® Antibodies for Cancer Therapy

Trifunctional Bispecific Antibodies Induce Tumor-Specific T Cells and Elicit a Vaccination Effect

“…F, frequency of Trp2-specific CD8 (12), disseminated tumor cells can effectively be killed (14). An important issue for constructing trifunctional bsAbs is the use of the isotype combination mouse IgG2a and rat IgG2b, because it was shown that this combination mediates interaction with activating, but not inhibitory, human FcgR (33). Several data described in this and in previous work indicate a similar FcgR binding of this isotype combination in the mouse (14).…”

“…To evaluate if these TAAs are targets for Surek-induced T cells, T cells from animals immunized with B78-D14 and Surek were restimulated in vitro and subsequently examined for IFN-g secretion in response to splenocytes that were loaded with the selected peptides. Specific recognition of 2 peptides from the MAGE-A family (MAGE-A5 [5][6][7][8][9][10][11][12] and MAGE-AX 169-176 ) and of the peptides p53 232-240 , gp100 [25][26][27][28][29][30][31][32][33] , and Trp2 180-188 was observed (Fig. 3E).…”

The Role of Relative Lymphocyte Count as a Biomarker for the Effect of Catumaxomab on Survival in Malignant Ascites Patients: Results from a Phase II/III Study

“…The trifunctional mode of action of catumaxomab occurs by binding to epithelial tumor cells via EpCAM to T cells via CD3 and activation of Fcg-receptor I-, IIa-, and IIIpositive accessory cells via its functional Fc domain (2)(3)(4)(5). The activation of different immune effector cells at the tumor site by catumaxomab leads to improved tumor cell elimination by a variety of immunologic killing mechanisms (4,6) and the presence of a functional immune system is key to its activity (7).…”

Design of in silico Trifunctional Antibody (hIgG1-FC: mouse-antiHER2× human-B7.1) Gene Cassettes and Expression Vectors: The Stage Prior to Production

“…In this work, the B7.1-IgV-like domain was used instead of anti-CD3 Ab due to its advantageous. It can direct CD28 cytotoxic T cells to kill tumor cells compared with the accessory cell-mediated killers such as macrophages, natural killer cells (NKC), and dendritic cells (DC) [5][6][7][8].…”

“…Tri-functional monoclonal antibodies (Triomab) belong to the first generation of bispecific antibodies (bsAbs) targeting two different epitopes [6,7], such as ertumaxomab which, in turn, targets tumoral HER2/Neu antigen (by antiHER2 domains), T-cell CD3 receptor epitopes (by anti-CD3 domains), and accessory cells such as natural killer cells (NK cells), contributing to destroy cells, (by antibody Fc) through antibody-dependent as well as complementdependent induction of cytotoxicity (ADCC and CDCC, respectively) [8][9][10]. Completing the phase I and II of clinical trials related to ertumaxomab and catumaxomab (Triomabs) [11,12] and the effective low dose range (microgram dose range versus milligram dose, i.e., high dose administration) in cancer therapy [7,10,13,14] have triggered the incentive of designing in silico specific expression vectors for the production of this class of antibodies. As functional diversity for mAb and triomab gets equal to 4/6 (x₁/n₁) and 6/6 (x₂/n₂), respectively, p gets equal to 10/12 (x₁+x₂)/(n₁+n₂) resulting z and |z| scores to get equal to -1.55 and 1.55, respectively, which is less than z scores equal to 1.96 (α=0.05) and 2.576 (α=0.01).…”