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.
Diagnostic and Molecular Health Care Group, Box 113 Veterans Affairs Medical Center, 5901 E. 7th Street, Long Beach, CA 90822, USA.
Ramon
R
Sanchez
Christopher
C
Williams
Jose L
JL
Daza
Qinghong
Q
Dan
Qingcheng
Q
Xu
Yijun
Y
Chen
Christina
C
Delgado
Neary
N
Arpajirakul
Edward W B
EW
Jeffes
Ronald C
RC
Kim
Thomas
T
Douglass
Usama
U
Al Atar
H
H
Terry Wepsic
Martin R
MR
Jadus
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