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.
Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America. Jabrah14@jhmi.edu
John M
JM
Abraham
Yulan
Y
Cheng
James P
JP
Hamilton
Bogdan
B
Paun
Zhe
Z
Jin
Rachana
R
Agarwal
Takatsugu
T
Kan
Stefan
S
David
Alexandru
A
Olaru
Jian
J
Yang
Tetsuo
T
Ito
Florin M
FM
Selaru
Yuriko
Y
Mori
Stephen J
SJ
Meltzer
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