Generation of small 32P-labeled peptides as a potential approach to colorectal cancer therapy.
Cancers have been revealed to be extremely heterogenous in terms of the frequency and types of mutations present in cells from different malignant tumors. Thus, it is likely that uniform clinical treatment is not optimal for all patients, and that the development of individualized therapeutic regimens may be beneficial. We describe the generation of multiple, unique small peptides nine to thirty-four amino acids in length which, when labeled with the radioisotope (32)P, bind with vastly differing efficiencies to cell lines derived from different colon adenocarcinomas. In addition, the most effective of these peptides permanently transfers the (32)P radioisotope to colorectal cancer cellular proteins within two hours at a rate that is more than 150 times higher than in cell lines derived from other cancers or from the normal tissues tested. Currently, the only two FDA-approved radioimmunotherapeutic agents in use both employ antibodies directed against the B cell marker CD20 for the treatment of non-Hodgkin's lymphoma. By using the method described herein, large numbers of different (32)P-labeled peptides can be readily produced and assayed against a broad spectrum of cancer types. This report proposes the development and use of (32)P-labeled peptides as potential individualized peptide-binding therapies for the treatment of colon adenocarcinoma patients.
Abraham
John M
JM
Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America. Jabrah14@jhmi.edu
Cheng
Yulan
Y
Hamilton
James P
JP
Paun
Bogdan
B
Jin
Zhe
Z
Agarwal
Rachana
R
Kan
Takatsugu
T
David
Stefan
S
Olaru
Alexandru
A
Yang
Jian
J
Ito
Tetsuo
T
Selaru
Florin M
FM
Mori
Yuriko
Y
Meltzer
Stephen J
SJ
D000230:Adenocarcinoma / Q000188:drug therapy*; D001345:Autoradiography; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D010455:Peptides / Q000627:therapeutic use*; D010761:Phosphorus Radioisotopes / Q000627:therapeutic use*; D010766:Phosphorylation
D010455:Peptides; D010761:Phosphorus Radioisotopes