Kelly A. King

Abstract

Several monoclonal antibody (MAb) types derived from mice have been developed specifically for the use of targeting human tumors. The specificity of these murine MAb’s for their respective tumor antigens is very high making them potentially good immunotherapeutic agents for cancer treatment and diagnosis. A limiting factor in using these murine MAb’s in patients is the development of human anti-mouse antibody (HAMA). The presence of HAMA may reduce the effectiveness of MAb for tumor targeting. If patient sensitization could be quickly detected following the initial infusion of MAb, then future infusion could be altered or terminated to prevent further sensitization. Interleukin-2 receptors (IL-2R) are expressed on the lymphocyte cell surface and released into serum soon after immune activation has begun. Another early sign of immune activation is lymphocyte proliferation. The detection of IL-2R production or increased lymphoproliferation in cancer patients receiving MAb infusion could help predict whether or not HAMA will be produced and therefore aid in the planning of therapy. In the present study, the immune response of 28 patients with disseminated cancer of the colon, lung, or breast was evaluated before and after infusion of radiolabelled murine MAb. Several healthy volunteers were tested simultaneously with the patients for control. IL-2R in plasma and on the lymphocyte cell surface, as well as lymphocyte proliferation, was analyzed in blood samples obtained from the patients at preinfusion and at 4 and 7 days postinfusion. HAMA results showed that 85% (11/13) of the tested patients were HAMA producers. A change in the level of IL- 2R in the plasma was noted after infusion in 63% of the tested patients. Flow cytometry analysis showed a significant decrease in the ability of MAb to induce IL- 2R expression on the surface of lymphocytes after infusion. However, this was not observed when phytohemagglutinin (PHA) was used as the stimulating agent. In contrast, the lymphoblastogenic response of patient’s cells to PHA (but not to MAb) was significantly lower when compared to cells from healthy subjects. A significant positive correlation was seen between PHA-induced responsiveness in the lymphoblastogenesis, IL-2R expression using either flow cytometry and visual grading of fluorescence and the data obtained when murine MAb was used as the stimulating agent. These results suggest that it may be possible to predict before and early after murine MAb infusion the intensity of the reaction against the infused murine MAb by using one or more of these other assays.

LLU Discipline

Microbiology

Department

Microbiology

School

Graduate School

First Advisor

Daila S. Gridley

Second Advisor

James D. Kettering

Third Advisor

Robert W. Teel

Degree Name

Master of Science (MS)

Degree Level

M.S.

Year Degree Awarded

1989

Date (Title Page)

6-1989

Language

English

Library of Congress/MESH Subject Headings

Radionuclide Imaging; Radioisotopes; Antibodies; Monoclonal; Neoplasms -- therapy

Type

Thesis

Page Count

vi; 44

Digital Format

PDF

Digital Publisher

Loma Linda University Libraries

Usage Rights

This title appears here courtesy of the author, who has granted Loma Linda University a limited, non-exclusive right to make this publication available to the public. The author retains all other copyrights.

Collection

Loma Linda University Electronic Theses and Dissertations

Collection Website

http://scholarsrepository.llu.edu/etd/

Repository

Loma Linda University. Del E. Webb Memorial Library. University Archives

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