CD70 as a therapeutic target in human malignancies.
BACKGROUND
Expression of CD70, a member of the tumor necrosis factor superfamily, is restricted to activated T and B lymphocytes and mature dendritic cells. CD70 has also been detected on hematological tumors and on carcinomas. The restricted expression pattern of CD70 in normal tissues and its widespread expression in various malignancies makes it an attractive target for antibody-based therapeutics. Investigations to exploit CD70 as a cancer target have lead to the identification of potential antibody-based clinical candidates. Anti-CD70 antibodies for therapeutic use have been developed and used to validate CD70 as a target for cancers. Antibodies are also used as a vehicle to deliver potent cytotoxic drugs to target CD70+ malignant cells. Both unconjugated antibodies and antibody-drug conjugates targeting CD70 have been tested in animal models of human cancers.


OBJECTIVE
To describe the expression of CD70 in cancer cells and the development of antibody-based therapies against CD70.


METHODS
A review of the available literature.


CONCLUSIONS
Humanized anti-CD70 antibodies have shown significant antitumor activity in preclinical xenograft models of cancer. Additionally, anti-CD70 antibody-drug conjugates exhibit potent antitumor activity in solid tumor xenograft models, confirming increased therapeutic efficacy through cytotoxic drug delivery. Thus, preclinical animal models have provided strong evidence that targeting CD70 either with unconjugated antibodies or with antibody-drug conjugates represents a promising approach to treat human malignancies.
Grewal
Iqbal S
IS
Seattle Genetics, Inc., Department of Preclinical Therapeutics, 21823 30th Drive SE, Bothell, Washington 98021, USA. igrewal@seagen.com
D000818:Animals; D000912:Antibodies, Neoplasm / Q000276:immunology / Q000378:metabolism; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D053282:CD27 Ligand / Q000096:biosynthesis / Q000276:immunology* / Q000378:metabolism*; D016503:Drug Delivery Systems / Q000379:methods*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000502:physiology; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism*
D000912:Antibodies, Neoplasm; D000970:Antineoplastic Agents; D053282:CD27 Ligand