Efficacy of an Anti-transferrin Receptor 1 Antibody Against AIDS-related Non-Hodgkin Lymphoma: A Brief Communication.
The transferrin receptor 1 (TfR1), also known as CD71, is a target for antibody-based cancer immunotherapy due to its high expression on the surface of cancer cells and its ability to internalize. We have previously developed a mouse/human chimeric IgG3 specific for human TfR1 genetically fused to avidin, as a vector to deliver biotinylated anticancer agents into malignant cells. However, we found that this fusion protein (ch128.1Av), and to a lesser extent the same antibody without avidin (ch128.1), exhibits direct cytotoxic activity in vitro against certain malignant hematopoietic cells through the induction of TfR1 degradation and lethal iron starvation. Importantly, both ch128.1 and ch128.1Av have also shown significant anticancer activity in 2 xenograft models of the B-cell malignancy multiple myeloma. It is interesting to note that ch128.1 exhibited superior anticancer activity in both models compared with ch128.1Av, even against malignant cells that show no sensitivity to ch128.1 in vitro. In the present study, we evaluated the efficacy of ch128.1 against an AIDS-related human Burkitt lymphoma cell line (2F7) to determine if ch128.1 can eliminate these cells in vitro and in an in vivo model of AIDS-related non-Hodgkin lymphoma (AIDS-NHL). Even though 2F7 cells expressed high TfR1 levels, these cells lacked sensitivity to the cytotoxicity induced by ch128.1 in vitro. However, ch128.1 showed significant anticancer activity against these AIDS-NHL cells in vivo by significantly prolonging the survival of immunodeficient mice bearing 2F7 tumors. Therefore, ch128.1 warrants further study as a candidate for the treatment of AIDS-NHL and other B-cell malignancies.
Departments of *Surgery, Division of Surgical Oncology †Obstetrics and Gynecology §Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at UCLA ‡UCLA AIDS Institute ∥Department of Epidemiology, UCLA Fielding School of Public Health ¶Jonsson Comprehensive Cancer Center #The Molecular Biology Institute, University of California, Los Angeles, CA.
Tracy R
TR
Daniels-Wells
Daniel P
DP
Widney
Lai Sum
LS
Leoh
Otoniel
O
Martínez-Maza
Manuel L
ML
Penichet
D000163:Acquired Immunodeficiency Syndrome / Q000150:complications / Q000188:drug therapy; D000818:Animals; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology / Q000627:therapeutic use*; D007167:Immunotherapy; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000209:etiology; D016513:Mice, SCID; D011990:Receptors, Transferrin / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome
D015703:Antigens, CD; D000970:Antineoplastic Agents; C068126:CD71 antigen; D007074:Immunoglobulin G; D011990:Receptors, Transferrin; D011993:Recombinant Fusion Proteins