Therapeutic anti-NLGP monoclonal antibody for carcinoembryonic antigen expressing tumors is nontoxic to Swiss and BALB/c mice.
A murine monoclonal antibody (mAb), 1C8 was developed against a novel glycoprotein NLGP and its unique property to recognize carcinoembryonic antigen (CEA) was reported. Utilizing this CEA recognizing property, 1C8 is successful to restrict the growth of CEA(+) murine and human cancers both in vitro and in vivo. Here, we have thoroughly evaluated the toxicity profile of this mAb 1C8 on different physiological systems of both tumor-free and tumor-bearing Swiss and BALB/c mice. Effective concentration (25 μg/mice) of 1C8 caused no behavioral changes in animals and no death was recorded. Moreover, little increase in the body and organ weights in all mice groups was noted. MAb 1C8 showed no adverse effect on the hematological system, but little hematostimulation was noticed, as evidenced by increased hemoglobin content, leukocyte count and lymphocyte numbers. Liver enzymes like alkaline phosphatase, SGOT, SGPT and nephrological products like urea and creatinine assessment confirmed no abnormalities in both hepatic and renal functions. Number of T cells, B cells, NK cells, macrophages and dendritic cells was upregulated in vivo by mAb treatment with significant downregulation of regulatory T cells. During this treatment serum levels of type 1 cytokines were upregulated over type 2 cytokines. This mAb 1C8 also did not induce any significant increase in antibody titer following treatment. Accumulated evidences from Swiss and BALB/c mice strongly suggest that this mAb 1C8 is completely safe, thus, can be recommended for further clinical trial for the therapy of CEA(+) tumors.
Clinical Biochemistry Unit, Chittaranjan National Cancer Institute (CNCI), 37, S. P. Mukherjee Road, Kolkata 700026, India; Department of Immunoregulation and Immunodiagnostics, Chittaranjan National Cancer Institute (CNCI), 37, S. P. Mukherjee Road, Kolkata 700026, India.
Arnab
A
Das
Department of Immunoregulation and Immunodiagnostics, Chittaranjan National Cancer Institute (CNCI), 37, S. P. Mukherjee Road, Kolkata 700026, India.
Bipasa
B
Mondal
Department of Immunoregulation and Immunodiagnostics, Chittaranjan National Cancer Institute (CNCI), 37, S. P. Mukherjee Road, Kolkata 700026, India.
Anamika
A
Bose
Department of Surgical Oncology and Medical Oncology, Chittaranjan National Cancer Institute (CNCI), 37, S. P. Mukherjee Road, Kolkata 700026, India.
Jaydip
J
Biswas
Department of Immunoregulation and Immunodiagnostics, Chittaranjan National Cancer Institute (CNCI), 37, S. P. Mukherjee Road, Kolkata 700026, India.
Rathindranath
R
Baral
Clinical Biochemistry Unit, Chittaranjan National Cancer Institute (CNCI), 37, S. P. Mukherjee Road, Kolkata 700026, India. Electronic address: psmarajit@hotmail.com.
Smarajit
S
Pal
D000818:Animals; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage / Q000627:therapeutic use / Q000633:toxicity*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use / Q000633:toxicity*; D031601:Azadirachta / Q000276:immunology*; D001522:Behavior, Animal / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002272:Carcinoembryonic Antigen / Q000276:immunology*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006023:Glycoproteins / Q000276:immunology*; D007677:Kidney Function Tests; D008111:Liver Function Tests; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D009929:Organ Size / Q000187:drug effects; D018515:Plant Leaves / Q000276:immunology; D016019:Survival Analysis
D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents; D002272:Carcinoembryonic Antigen; D016207:Cytokines; D006023:Glycoproteins
Anti-NLGP mAb; Antibody response; CEA; Histology; Toxicity