PMID- 7803791
OWN - NLM
STAT- MEDLINE
DCOM- 19950202
LR  - 20210216
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 85
IP  - 1
DP  - 1995 Jan 1
TI  - Interleukin-2-transduced lymphocytes grow in an autocrine fashion and remain 
      responsive to antigen.
PG  - 139-45
AB  - The maintenance of T lymphocytes in vivo after adoptive transfer for 
      immunotherapy requires the systemic administration of interleukin-2 (IL-2), but 
      prolonged administration of IL-2 is associated with substantial toxicity. The 
      constitutive production of IL-2 by T cells may be an alternative method to 
      prolong T-cell survival and potentially augment antitumor responses. To study the 
      effects of constitutive production of IL-2 on the growth and antigen reactivity 
      of a murine T cell, the sperm-whale myoglobin (SWM) specific T-cell line 14.1 was 
      retrovirally transduced with the cDNA for IL-2. Cells that were transduced with 
      vectors without an internal promoter were able to proliferate in the absence of 
      exogenously added IL-2, and to grow in an autocrine fashion. These vectors used 
      an internal ribosomal entry site (IRES) to allow translation of the neomycin 
      phosphotransferase (neor) gene. In contrast, the cells transduced with an IL-2 
      vector in which the neor gene was under the transcriptional control of an 
      internal SV-40 promoter failed to proliferate or grow in the absence of 
      exogenously added IL-2. The proliferation of the cells growing without IL-2 could 
      be inhibited with antibodies to the IL-2 receptor or to human IL-2, indicating 
      that they were still IL-2 dependent. Despite their autocrine growth, no tumor 
      formation was observed in syngeneic mice injected subcutaneously with the 
      transduced cells, and the cells retained their antigen reactivity and 
      specificity. These results suggest that autocrine growth of T cells for therapy 
      will not interfere with effector function.
FAU - Treisman, J
AU  - Treisman J
AD  - Surgery Branch, National Cancer Institute, National Institutes of Health, 
      Bethesda, MD 20892.
FAU - Hwu, P
AU  - Hwu P
FAU - Minamoto, S
AU  - Minamoto S
FAU - Shafer, G E
AU  - Shafer GE
FAU - Cowherd, R
AU  - Cowherd R
FAU - Morgan, R A
AU  - Morgan RA
FAU - Rosenberg, S A
AU  - Rosenberg SA
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Antibodies)
RN  - 0 (DNA, Complementary)
RN  - 0 (Interleukin-2)
RN  - 0 (Receptors, Interleukin-2)
SB  - IM
MH  - Animals
MH  - Antibodies/pharmacology
MH  - Base Sequence
MH  - Cell Division/drug effects
MH  - DNA, Complementary/genetics
MH  - Female
MH  - *Gene Transfer Techniques
MH  - Genetic Vectors
MH  - Interleukin-2/*genetics/immunology/physiology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Molecular Sequence Data
MH  - Receptors, Interleukin-2/immunology/physiology
MH  - Repetitive Sequences, Nucleic Acid
MH  - Retroviridae/genetics
MH  - T-Lymphocytes/*immunology
EDAT- 1995/01/01 00:00
MHDA- 1995/01/01 00:01
CRDT- 1995/01/01 00:00
PHST- 1995/01/01 00:00 [pubmed]
PHST- 1995/01/01 00:01 [medline]
PHST- 1995/01/01 00:00 [entrez]
AID - S0006-4971(20)69781-6 [pii]
PST - ppublish
SO  - Blood. 1995 Jan 1;85(1):139-45.