Journal: Frontiers in Oncology

Article Title: Improving CD3 bispecific antibody therapy in solid tumors using combination strategies

doi: 10.3389/fonc.2025.1548446

Figure Lengend Snippet: FDA-approved CD3 bispecific therapies.

Article Snippet: Blinatumomab , Amgen , CD3xCD19 , BiTE , Hematological , Acute Lymphoblastic Leukemia , Dec 2014 , ( ) .

Techniques:

Journal: mAbs

Article Title: A pivotal decade for bispecific antibodies?

doi: 10.1080/19420862.2024.2321635

Figure Lengend Snippet: Approved bsAbs and bsAbs under regulatory review.

Article Snippet: From 2009 to 2020, only two additional bsAbs were approved: (1) in 2014, the Fc-free tandem single-chain variable fragment (scFv)-based CD19/CD3ε bispecific T cell engager (BiTE) blinatumomab (Amgen) for the treatment of acute lymphoblastic leukemia (ALL), and (2) in 2017, the humanized hetero-dimeric coagulation factor IXa/X bispecific ART-Ig emicizumab (Roche group), which acts as a Factor VIII mimetic for the treatment of hemophilia A ( )., Figure 1.

Techniques:

Journal: Molecular Therapy Oncolytics

Article Title: CD3 engagement as a new strategy for allogeneic “off-the-shelf” T cell therapy

doi: 10.1016/j.omto.2022.02.024

Figure Lengend Snippet: BiTE-T cells have decreased CD3/TCRαβ expression and alloreactivity (A) CD3/TCRαβ expression on human T cells treated with human CD19 BiTE (blinatumomab) in the presence of 3T3.mCD19 (left) or 3T3.hCD19 cells (right). (B) CD3/TCRαβ expression on CD19 or Her2 BiTE-T cells. (C) T cell activation and cytokine production after TCRαβ stimulation. (D–G) GvHD risk evaluation of BiTE-T cells. Male NSG mice received cyclophosphamide (CTX) or whole-body irradiation (TBI) first and then 10 million T cells 1 day after. Mice were monitored for GvHD. (D) Study design. (E) Weight change over time. (F) NSG mice survival. (G) T cell persistence in peripheral blood. (H) CD3/TCRαβ expression on CD19 BiTE-T cells in peripheral blood of NSG mice without targets. (I) CD3/TCRαβ expression over time on Her2 BiTE-T cells in peripheral blood of NSG mice without targets. (J) CD3/TCRαβ expression on CD19 BiTE-T cells in serial-killing assay on CD19-expressing NALM6 cells. (K) CD3/TCRαβ expression on Her2 BiTE-T cells in serial killing assay on A375.Her2 cells. (L and M) CD3/TCRαβ expression on Her2-targeting T cells in vivo . NSG mice were subcutaneously injected with A375.Her2 cells and treated with Her2 BiTE-T or CAR-T cells 8–10 days later. (L) CD3/TCRαβ expression on donor T cells in peripheral blood 3 weeks after T cell injection. (M) CD3/TCRαβ expression of tumor infiltrating T cells 4 weeks after T cell injection in the A375.Her2 solid-tumor model. (N) CD3/TCRαβ expression on co-cultured T cells. BiTE-T or CAR-T cells from one healthy donor (as donor T cells) were co-cultured with activated T cells from another healthy donor (as recipient T cells) for 72 h and subjected to flow cytometry. DTC, donor T cells; RTC, recipient T cells. (O) CD3/TCRαβ expression over time on host and donor T cells in allogeneic MLR assay. CD19 BiTE-T or CAR-T cells were co-cultured with HLA-mismatched PBMCs at a 1:10 E:T ratio in 96-well plates, and CD3/TCRαβ expression on host and donor T cells were followed over time. Data are presented as means ± SD. ∗p<0.05; ∗∗p<0.01; ∗∗∗p<0.001; ∗∗∗∗p<0.0001; ns, not significant.

Article Snippet: For BiTE stimulation, human CD19 BiTE (blinatumomab) was purchased from BPS Bioscience (San Diego, CA).

Techniques: Expressing, Activation Assay, Irradiation, In Vivo, Injection, Cell Culture, Flow Cytometry, Mlr Assay

Journal: Molecular Therapy Oncolytics

Article Title: CD3 engagement as a new strategy for allogeneic “off-the-shelf” T cell therapy

doi: 10.1016/j.omto.2022.02.024

Figure Lengend Snippet: BiTE-T cells produce fewer cytokines and are comparable to or better than CAR-T cells on efficacy in the presence of host T cells (A and B) Cytotoxicity (A) and cytokine production (B) of CD19 BiTE-T or CAR-T cells against 3T3.hCD19 cells. (C and D) Cytotoxicity (C) and cytokine production (D) of Her2 BiTE-T or CAR-T cells against A375.Her2 cells. (E–H) a comparison study of CD19 BiTE-T and CAR-T cells in vivo with host T cell presence. (E) Study design. Male NSG mice received 1.2 Gy full-body irradiation and then were engrafted with 7 million HLA-A2+-activated T cells 1 day after. Nalm6GL cells were given at day 0. Mice were treated with HLA-A2– CD19 BiTE-T or CAR-T cells at day 3. Survival (F), Donor T cells (DTC; G), and recipient T cells (RTC; H) in peripheral blood were monitored over time. (I–L) a comparison study of Her2 BiTE-T and CAR-T cells in vivo with host T cell presence. (I) Study design. Male NSG mice received 1.2 Gy full-body irradiation and then were engrafted with 5 million HLA-A2+-activated T cells 1 day after. A375.Her2 cells were given at day 0. Mice were treated with HLA-A2– Her2 BiTE-T or CAR-T cells at day 8. Tumor growth (J), DTC (K), and RTC (L) in peripheral blood were monitored over time. Data are presented as means ± SD. ∗p<0.05; ∗∗p<0.01; ∗∗∗p<0.001; ∗∗∗∗p<0.0001; ns, not significant.

Article Snippet: For BiTE stimulation, human CD19 BiTE (blinatumomab) was purchased from BPS Bioscience (San Diego, CA).

Techniques: In Vivo, Irradiation

Journal: Molecular Therapy Oncolytics

Article Title: CD3 engagement as a new strategy for allogeneic “off-the-shelf” T cell therapy

doi: 10.1016/j.omto.2022.02.024

Figure Lengend Snippet: Co-expressing co-stimulatory factors or cytokines enhances BiTE-T cells to match or overperform CAR-T cells (A–C) a serial-killing assay on A375.Her2 cells. (A) T cell proliferation over time. (B) TCRαβ expression over time. (C) CD3 expression over time. (D–H) efficacy comparison of co-stimulation-enhanced Her2 BiTE-T and CAR-T cells. (D) Study design. (E) Tumor growth. (F) Percentages of tumor-infiltrating T cells. (G) Donor T cells in peripheral blood over time. (H) Weight change over time. (I–M) Data from a comparison study of co-stimulation-enhanced CD19 BiTE-T and CAR-T cells. (I) Study design. (J) Survival. Small arrows indicate death events unrelated to leukemia or GvHD. (K) Weight change. (L) Donor T persistence in peripheral blood. (M) CD3/TCRαβ expression on week 4 blood T cells. (N) Proliferation of Her2 targeting cytokine -enhanced BiTE-T cells in serial-killing assay in vitro . (O) Proliferation of CD19 targeting cytokine-enhanced BiTE-T cells in serial-killing assay in vitro . Data are presented as means ± SD. ∗p<0.05; ∗∗p<0.01; ∗∗∗p<0.001; ∗∗∗∗p<0.0001; ns, not significant.

Article Snippet: For BiTE stimulation, human CD19 BiTE (blinatumomab) was purchased from BPS Bioscience (San Diego, CA).

Techniques: Expressing, In Vitro

Journal: Cancer Drug Resistance

Article Title: Therapeutics to harness the immune microenvironment in multiple myeloma

doi: 10.20517/cdr.2022.23

Figure Lengend Snippet: Effects of FDA-approved and investigational agents on the myeloma immune microenvironment

Article Snippet: The prototypical BiTE- blinatumumab (Glaxo-Smith Kline) targets CD3 and CD19 to facilitate T cell-mediated killing of relapsed acute lymphocytic leukemia (ALL) cells [ ] [ , ] .

Techniques: Bioprocessing, Activation Assay, In Vitro, Expressing, Activity Assay