|
|
 Previous Article | Table of Contents | Next Article 
Adoptive transfer of anti-CD3-activated CD4+ T cells plus cyclophosphamide
and liposome-encapsulated interleukin-2 cure murine MC- 38 and 3LL tumors
and establish tumor-specific immunity
ML Saxton, DL Longo, HE Wetzel, H Tribble, WG Alvord, LW Kwak, AS Leonard, CD Ullmann, BD Curti and AC Ochoa
Biological Response Modifiers Program, National Cancer Institute, Frederick
Cancer Research and Development Center, MD, USA.
The infusion of anti-CD3-activated murine T cells plus interleukin-2 (IL-2)
exerts antitumor effects against several tumors in murine immunotherapy
models. This study compares the therapeutic efficacy of anti-CD3-activated
CD4+ or CD8+ T-cell subsets, when given with cyclophosphamide (Cy) and
liposome-encapsulated IL-2 (L-IL2) in a murine model. C57BL/6 mice bearing
subcutaneous (S.C.) MC-38 colon adenocarcinoma, 3LL Lewis lung carcinoma,
or 38C13 lymphoma for 7 to 14 days were pretreated with low-dose
intraperitoneal (I.P.) Cy before intravenous (I.V.) injection of
anti-CD3-activated T cells or T-cell subsets. Cell administration was
followed by I.P. administration of L- IL2 for 5 days. Mice receiving
activated CD4+ T cells showed significantly reduced tumor growth or
complete remissions with prolonged disease-free survival in MC-38, 3LL, and
38C13. The timing of Cy doses in relation to adoptive transfer was critical
in obtaining the optimal antitumor effect by CD4+ cells. Injecting Cy 4
days before the infusion of CD4+ cells greatly enhanced the antitumor
effect of the CD4+ cells and improved survival of the mice compared with
other Cy regimens. C57BL/6 mice cured of MC-38 after treatment with CD4+ T
cells developed tumor-type immunologic memory as demonstrated by their
ability to reject rechallenges with MC-38, but not 3LL. Similarly, mice
cured of 3LL tumors rejected rechallenges of 3LL, but not MC-38. The
immunologic memory could be transferred with an I.V. injection of
splenocytes from mice cured of MC-38 or 3LL. No cytotoxic T-lymphocyte
activity was detected in T cells or T-cell subsets from mice cured of MC-38
or 3LL. Increased IL-2 and interferon-gamma (IFN-gamma) production was
observed from CD4+ subsets in cured animals when stimulated in vitro with
the original tumor, but not with an unrelated syngeneic tumor. These
results suggest that tumor-specific immunity can be achieved in vivo with
anti-CD3-stimulated CD4+ T cells in this cellular therapy model.
Volume 89,
Issue 7,
pp. 2529-2536,
04/01/1997
Copyright © 1997 by The American Society of Hematology
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
K. Chamoto, T. Tsuji, H. Funamoto, A. Kosaka, J. Matsuzaki, T. Sato, H. Abe, K. Fujio, K. Yamamoto, T. Kitamura, et al.
Potentiation of Tumor Eradication by Adoptive Immunotherapy with T-cell Receptor Gene-Transduced T-Helper Type 1 Cells
Cancer Res.,
January 1, 2004;
64(1):
386 - 390.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Pelaez, J. A. Campillo, J. A. Lopez-Asenjo, and J. L. Subiza
Cyclophosphamide Induces the Development of Early Myeloid Cells Suppressing Tumor Cell Growth by a Nitric Oxide-Dependent Mechanism
J. Immunol.,
June 1, 2001;
166(11):
6608 - 6615.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Baker, M. R. Verneris, M. Ito, J. A. Shizuru, and R. S. Negrin
Expansion of cytolytic CD8+ natural killer T cells with limited capacity for graft-versus-host disease induction due to interferon {gamma} production
Blood,
May 15, 2001;
97(10):
2923 - 2931.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Schiavoni, F. Mattei, T. Di Pucchio, S. M. Santini, L. Bracci, F. Belardelli, and E. Proietti
Cyclophosphamide induces type I interferon and augments the number of CD44hi T lymphocytes in mice: implications for strategies of chemoimmunotherapy of cancer
Blood,
March 15, 2000;
95(6):
2024 - 2030.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Rodolfo, C. Zilocchi, P. Accornero, B. Cappetti, I. Arioli, and M. P. Colombo
IL-4-Transduced Tumor Cell Vaccine Induces Immunoregulatory Type 2 CD8 T Lymphocytes That Cure Lung Metastases Upon Adoptive Transfer
J. Immunol.,
August 15, 1999;
163(4):
1923 - 1928.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
