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Title: Lymphokine-activated killer (LAK) cells can be focused at sites of tumor growth by products of macrophage activation

Abstract

Successful adoptive cancer immunotherapy presumably depends on the accumulation of tumoricidal leukocytes at the sites of tumor growth. Large numbers of lymphokine-activated killer (LAK) cells can be generated in vitro by growth in high concentrations of interleukin-2 (IL-2), but relatively few arrive at the tumor site after intravenous injection. We hypothesize that the delivery of LAK cells to tumor sites may be augmented by previously demonstrated lymphocyte-recruiting factors, including activated macrophage products such as interleukin-1 (IL-1) and tumor necrosis factor. /sup 111/Indium-labeled LAK cells were injected intravenously into syngeneic mice bearing the macrophage activator endotoxin (LPS) in one hind footpad, and saline solution was injected into the contralateral footpad. Significantly more activity was recovered from the LPS-bearing footpad at all times during a 96-hour period. Recombinant IL-1 also attracted more LAK cells after injection into tumor-free hind footpads. Furthermore, LAK cells preferentially homed to hind footpads that were bearing 3-day established sarcomas after intralesional injections of LPS, IL-1, or tumor necrosis factor when compared with contralateral tumor-bearing footpads injected with saline solution alone. In preliminary experiments, mice with hind-footpad tumors appeared to survive longer after combined systemic IL-2 and LAK therapy if intralesional LPS was administered. These studies demonstrate thatmore » macrophage activation factors that have been shown capable of attracting circulating normal lymphocytes can also effectively attract LAK cells from the circulation. By the stimulation of macrophages at the sites of tumor growth, more LAK cells can be attracted. It is hoped that by focusing the migration of LAK cells to tumors, LAK cells and IL-2 would effect tumor regression more efficiently and with less toxicity.« less

Authors:
; ; ; ; ; ;
Publication Date:
Research Org.:
Univ. of Minnesota Hospitals, Minneapolis
OSTI Identifier:
6244044
Resource Type:
Journal Article
Journal Name:
Surgery; (United States)
Additional Journal Information:
Journal Volume: 102:2
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; 62 RADIOLOGY AND NUCLEAR MEDICINE; LYMPHOCYTES; BIOLOGICAL LOCALIZATION; LABELLING; SARCOMAS; IMMUNOTHERAPY; CELL KILLING; EXPERIMENTAL NEOPLASMS; GROWTH FACTORS; INDIUM 111; INTRAVENOUS INJECTION; LIPOPOLYSACCHARIDES; LYMPHOKINES; MACROPHAGES; MICE; TRACER TECHNIQUES; ANIMAL CELLS; ANIMALS; BETA DECAY RADIOISOTOPES; BIOLOGICAL MATERIALS; BLOOD; BLOOD CELLS; BODY FLUIDS; CARBOHYDRATES; CONNECTIVE TISSUE CELLS; DAYS LIVING RADIOISOTOPES; DISEASES; ELECTRON CAPTURE RADIOISOTOPES; INDIUM ISOTOPES; INJECTION; INTAKE; INTERMEDIATE MASS NUCLEI; ISOMERIC TRANSITION ISOTOPES; ISOTOPE APPLICATIONS; ISOTOPES; LEUKOCYTES; LIPIDS; MAMMALS; MATERIALS; MINUTES LIVING RADIOISOTOPES; MITOGENS; NEOPLASMS; NUCLEI; ODD-EVEN NUCLEI; ORGANIC COMPOUNDS; PHAGOCYTES; POLYSACCHARIDES; PROTEINS; RADIOISOTOPES; RODENTS; SACCHARIDES; SOMATIC CELLS; THERAPY; VERTEBRATES; 550901* - Pathology- Tracer Techniques; 550600 - Medicine

Citation Formats

Migliori, R J, Gruber, S A, Sawyer, M D, Hoffman, R, Ochoa, A, Bach, F H, and Simmons, R L. Lymphokine-activated killer (LAK) cells can be focused at sites of tumor growth by products of macrophage activation. United States: N. p., 1987. Web.
Migliori, R J, Gruber, S A, Sawyer, M D, Hoffman, R, Ochoa, A, Bach, F H, & Simmons, R L. Lymphokine-activated killer (LAK) cells can be focused at sites of tumor growth by products of macrophage activation. United States.
Migliori, R J, Gruber, S A, Sawyer, M D, Hoffman, R, Ochoa, A, Bach, F H, and Simmons, R L. 1987. "Lymphokine-activated killer (LAK) cells can be focused at sites of tumor growth by products of macrophage activation". United States.
@article{osti_6244044,
title = {Lymphokine-activated killer (LAK) cells can be focused at sites of tumor growth by products of macrophage activation},
author = {Migliori, R J and Gruber, S A and Sawyer, M D and Hoffman, R and Ochoa, A and Bach, F H and Simmons, R L},
abstractNote = {Successful adoptive cancer immunotherapy presumably depends on the accumulation of tumoricidal leukocytes at the sites of tumor growth. Large numbers of lymphokine-activated killer (LAK) cells can be generated in vitro by growth in high concentrations of interleukin-2 (IL-2), but relatively few arrive at the tumor site after intravenous injection. We hypothesize that the delivery of LAK cells to tumor sites may be augmented by previously demonstrated lymphocyte-recruiting factors, including activated macrophage products such as interleukin-1 (IL-1) and tumor necrosis factor. /sup 111/Indium-labeled LAK cells were injected intravenously into syngeneic mice bearing the macrophage activator endotoxin (LPS) in one hind footpad, and saline solution was injected into the contralateral footpad. Significantly more activity was recovered from the LPS-bearing footpad at all times during a 96-hour period. Recombinant IL-1 also attracted more LAK cells after injection into tumor-free hind footpads. Furthermore, LAK cells preferentially homed to hind footpads that were bearing 3-day established sarcomas after intralesional injections of LPS, IL-1, or tumor necrosis factor when compared with contralateral tumor-bearing footpads injected with saline solution alone. In preliminary experiments, mice with hind-footpad tumors appeared to survive longer after combined systemic IL-2 and LAK therapy if intralesional LPS was administered. These studies demonstrate that macrophage activation factors that have been shown capable of attracting circulating normal lymphocytes can also effectively attract LAK cells from the circulation. By the stimulation of macrophages at the sites of tumor growth, more LAK cells can be attracted. It is hoped that by focusing the migration of LAK cells to tumors, LAK cells and IL-2 would effect tumor regression more efficiently and with less toxicity.},
doi = {},
url = {https://www.osti.gov/biblio/6244044}, journal = {Surgery; (United States)},
number = ,
volume = 102:2,
place = {United States},
year = {Sat Aug 01 00:00:00 EDT 1987},
month = {Sat Aug 01 00:00:00 EDT 1987}
}