Immunotherapeutic perspective for bispecific antibodies

Bispecific antibody targeting of doxorubicin to carcinoembryonic antigen-expressing colon cancer cell linesin vitro andin vivo

“…There are many potential uses for BsMAbs; 7,8 e.g., by using a BsMAb that recognises both a molecule expressed on tumour cells and a chemotherapeutic drug, it should be possible to target the drug to the tumour, thereby obviating the need for the complex chemistry required to directly link the antibody carrier to the cytotoxic agent. Our objective was to evaluate the efficacy of a BsMAb recognising CEA and the clinically effective drug Dox in targeting Dox to CEA-expressing human colon cancer cell lines in vitro and in vivo.…”

“…6 In a complementary approach, bispecific antibodies (BsMAbs) are being developed as novel bioconjugates 7,8 that recognise a tumour-associated target with one antigen-binding site and a variety of molecules with the other antigen-binding site, including molecules on cells of the immune system, 9 -12 toxins 13,14 and cytokines. 15 We have previously reported production of immunoconjugates of the chemotherapeutic drug doxorubicin (Dox) with an anti-carcinoembryonic antigen (CEA) MAb 16,17 and production of BsMAbs recognising CEA and Dox.…”

Effect of tetravalent bispecific CD19×CD3 recombinant antibody construct and CD28 costimulation on lysis of malignant B cells from patients with chronic lymphocytic leukemia by autologous T cells

“…An emerging approach is the retargeting of cellular effector systems, such as T cells, by bispecific antibodies. 8 However, progress in research and development into the clinical applications of these immunotherapeutic agents has been significantly slowed by problems of manufacturing, immunogenicity of mouse-derived antibodies, lack of therapeutic efficacy, toxicity associated with cytokine storms and unfavorable pharmacokinetics. 9 To improve the therapeutic potential of bispecific antibodies, we constructed a novel recombinant molecule named "tandem diabody" (tanDb), which is bispecific and tetravalent.…”

“…7 One of the alternative immunotherapeutic strategies is based on activation of host immune mechanisms using bispecific antibodies. 8,9 The bispecific antibody makes a bridge between the tumor cell and the immune effector cell, triggering cytotoxic responses. For B-CLL, the B-cell marker CD19 is one of the best targets since it is profusely expressed on leukemic cells and is not shed or internalized by B-CLL cells.…”

“…10 One of the best-studied cytotoxic triggering receptors is a multichain TCR/CD3 signaling complex on T cells. 8 To date, different forms of the CD19ϫCD3 bispecific antibody have been generated and used in a number of in vitro and in vivo therapeutic studies. [11][12][13][14][15][16][17][18] These bispecific antibodies have been produced using either rodent hybrid hybridomas, 12,14 chemical crosslinking of 2 MAbs 11 or recombinant antibody Abbreviations: ADCC, antibody-dependent cellular cytotoxicity; BrdU, bromodeoxyuridine; BsDb, bispecific diabody; CD, cluster of differentiation; CLL, chronic lymphocytic leukemia; CTLA-4, cytotoxic T lymphocyte-associated antigen 4; EC 50 , half-maximal effective concentration; HS, human serum; MAb, monoclonal antibody; NHL, non-Hodgkin's lymphoma; PBL, peripheral blood lymphocyte; PBMC, peripheral blood mononuclear cell; scBsDb, single-chain BsDb; scFv, single-chain variable fragment of antibody; tanDb, tandem diabody; TCR, T-cell receptor; TNF, tumor necrosis factor; TRAIL, TNF-␣-related apoptosis-inducing ligand; V H , variable domain of the heavy chain of an antibody; V L , variable domain of the light chain of an antibody; WBC, white blood count.…”