T9 glioma cells expressing membrane-macrophage colony stimulating factor produce CD4+ T cell-associated protective immunity against T9 intracranial gliomas and systemic immunity against different syngeneic gliomas.
Cloned T9 glioma cells (T9-C2) expressing the membrane form of macrophage colony stimulating factor (mM-CSF) inoculated subcutaneously into rats do not grow and glioma-specific immunity is stimulated. Immunotherapy experiments showed that intracranial T9 tumors present for one to four days could be successfully eradicated by peripheral vaccination with T9-C2 cells. CD4+ and CD8+ T splenocytes from immunized rats, when restimulated in vitro with T9 cells, produced interleukin-2 and -4. Protective immunity against intracranial T9 gliomas could only be adoptively transferred into naive rats by the CD4+ splenocytes obtained from T9-C2 immunized rats. Rats immunized by the T9-C2 tumor cells also resisted two different syngeneic gliomas (RT2 and F98) but allowed a syngeneic NUTU-19 ovarian cancer to grow. Such cross-protective immunity against unrelated gliomas suggests that mM-CSF transfected tumor cells have immunotherapeutic potential for use as an allogeneic tumor vaccine.
Sanchez
Ramon
R
Diagnostic and Molecular Health Care Group, Box 113 Veterans Affairs Medical Center, 5901 E. 7th Street, Long Beach, CA 90822, USA.
Williams
Christopher
C
Daza
Jose L
JL
Dan
Qinghong
Q
Xu
Qingcheng
Q
Chen
Yijun
Y
Delgado
Christina
C
Arpajirakul
Neary
N
Jeffes
Edward W B
EW
Kim
Ronald C
RC
Douglass
Thomas
T
Al Atar
Usama
U
Terry Wepsic
H
H
Jadus
Martin R
MR
D019264:Adoptive Transfer; D000818:Animals; D001932:Brain Neoplasms / Q000276:immunology* / Q000517:prevention & control / Q000648:ultrastructure; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D002478:Cells, Cultured; D002999:Clone Cells; D005260:Female; D005910:Glioma / Q000276:immunology* / Q000517:prevention & control / Q000648:ultrastructure; D007376:Interleukin-2 / Q000096:biosynthesis / Q000235:genetics; D015847:Interleukin-4 / Q000096:biosynthesis / Q000235:genetics; D007700:Kinetics; D016173:Macrophage Colony-Stimulating Factor / Q000235:genetics* / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D009368:Neoplasm Transplantation; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011916:Rats, Inbred F344; D016019:Survival Analysis; D014162:Transfection; D014407:Tumor Cells, Cultured
D007376:Interleukin-2; D008565:Membrane Proteins; D012333:RNA, Messenger; D015847:Interleukin-4; D016173:Macrophage Colony-Stimulating Factor