Lymphokine-activated killer (LAK) cells can be focused at sites of tumor growth by products of macrophage activation
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.
- Research Organization:
- Univ. of Minnesota Hospitals, Minneapolis
- OSTI ID:
- 6244044
- Journal Information:
- Surgery; (United States), Vol. 102:2
- Country of Publication:
- United States
- Language:
- English
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LYMPHOCYTES
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LABELLING
SARCOMAS
IMMUNOTHERAPY
CELL KILLING
EXPERIMENTAL NEOPLASMS
GROWTH FACTORS
INDIUM 111
INTRAVENOUS INJECTION
LIPOPOLYSACCHARIDES
LYMPHOKINES
MACROPHAGES
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BIOLOGICAL MATERIALS
BLOOD
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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
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RODENTS
SACCHARIDES
SOMATIC CELLS
THERAPY
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550901* - Pathology- Tracer Techniques
550600 - Medicine