PMID- 10202049
OWN - NLM
STAT- MEDLINE
DCOM- 19990506
LR  - 20171116
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 162
IP  - 8
DP  - 1999 Apr 15
TI  - 4-1BBL cooperates with B7-1 and B7-2 in converting a B cell lymphoma cell line
      into a long-lasting antitumor vaccine.
PG  - 5003-10
AB  - A20 is a B cell lymphoma that constitutively expresses the costimulatory molecule
      B7-2 yet grows readily as a tumor in syngeneic BALB/c mice. We have compared the 
      tumorigenicity of A20 variants expressing either B7-1 (A20/B7-1) or B7-2
      (A20/B7-2) with an A20 variant expressing B7-1 and B7-2 with 4-1BBL (A20/4-1BBL),
      a costimulatory member of the TNF family. Mice injected with tumors expressing
      the vector backbone (A20/CMV) or B7-1 developed tumors within 25 days of s.c.
      injection. In contrast, mice injected with A20/4-1BBL were tumor free for the
      150-day follow-up period, while 25% of mice injected with A20/B7-2 developed
      tumors. Tumorigenicity experiments using nude mice indicated the requirement for 
      T cells for variant rejection. Almost all mice that resisted the initial tumor
      challenge were resistant to further challenge with the parental tumor.
      Splenocytes from these mice showed high CTL lytic activity against the parental
      tumor, A20, as well as the syngeneic BALB/c lymphoma K46J, but showed background 
      levels of lytic activity against the congenic SCID thymoma line ST-D2 or the
      allogeneic EL4 thymoma. In vitro blocking experiments with anti-B7-1 plus
      anti-B7-2 and/or soluble 4-1BB receptor showed B7-1, B7-2, and 4-1BBL all
      contributed to the CTL activity. Thus, the data show that neither B7-1 or B7-2
      alone can confer full immunogenicity to the A20 lymphoma but that the addition of
      4-1BBL results in a tumor that is highly immunogenic and can confer long-lasting 
      protection against challenge with parental tumor in vivo.
FAU - Guinn, B A
AU  - Guinn BA
AD  - Department of Immunology, Institute of Medical Sciences, University of Toronto,
      Ontario, Canada.
FAU - DeBenedette, M A
AU  - DeBenedette MA
FAU - Watts, T H
AU  - Watts TH
FAU - Berinstein, N L
AU  - Berinstein NL
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (4-1BB Ligand)
RN  - 0 (Antigens, CD)
RN  - 0 (B7-1 Antigen)
RN  - 0 (B7-2 Antigen)
RN  - 0 (Cancer Vaccines)
RN  - 0 (Cd86 protein, mouse)
RN  - 0 (Interleukin-2)
RN  - 0 (Ligands)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Tnfsf9 protein, mouse)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 207137-56-2 (Interleukin-4)
SB  - AIM
SB  - IM
MH  - 4-1BB Ligand
MH  - Animals
MH  - Antigens, CD/*physiology
MH  - B7-1 Antigen/*physiology
MH  - B7-2 Antigen
MH  - CD4-Positive T-Lymphocytes/metabolism
MH  - Cancer Vaccines/genetics/*immunology
MH  - Clone Cells
MH  - Cloning, Molecular
MH  - Cytotoxicity, Immunologic
MH  - Drug Synergism
MH  - Female
MH  - Gene Expression/immunology
MH  - Immunophenotyping
MH  - Immunotherapy, Adoptive/*methods
MH  - Interleukin-2/biosynthesis
MH  - Interleukin-4/biosynthesis
MH  - Ligands
MH  - Lymphocyte Culture Test, Mixed
MH  - Lymphoma, B-Cell/genetics/*immunology/*prevention & control
MH  - Membrane Glycoproteins/*physiology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - Mice, SCID
MH  - T-Lymphocytes, Cytotoxic/immunology
MH  - Tumor Cells, Cultured
MH  - Tumor Necrosis Factor-alpha/biosynthesis/genetics/*physiology
EDAT- 1999/04/14 00:00
MHDA- 1999/04/14 00:01
CRDT- 1999/04/14 00:00
PHST- 1999/04/14 00:00 [pubmed]
PHST- 1999/04/14 00:01 [medline]
PHST- 1999/04/14 00:00 [entrez]
PST - ppublish
SO  - J Immunol. 1999 Apr 15;162(8):5003-10.