Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1995-9-12
pubmed:abstractText
Bifunctional Abs (BFA) with specificity for the TCR/CD3 complex of T cells and tumor Ag can bridge T lymphocytes and tumor cells and, thereby, trigger activation events. The ability of intact and F(ab')2 anti-CD3 (500A2) x anti-p97 (96.5) BFA to induce activation of T lymphocytes in the presence of murine melanoma tumor cells (CL-62) expressing human melanoma-associated Ag (p97) was investigated in vitro and in vivo. Intact and F(ab')2 BFA induced significant proliferation of T lymphocytes in the presence of p97+ tumor cells. Incubation of splenocytes with intact or F(ab')2 BFA and p97+ tumor cells increased BFA-mediated cytotoxicity against relevant tumor cells. Intact BFA, in contrast to F(ab')2 BFA, induced some activation of T cells in vitro even in the absence of p97+ target cells. In nontumor-bearing mice, administration of F(ab')2 BFA, in contrast to intact BFA, did not increase cytotoxic activity of lymph node (LN) cells and splenocytes. However, when F(ab')2 BFA was administrated into CL-62-bearing mice, an increase of BFA-mediated cytotoxicity of tumor-infiltrating lymphocytes, but not splenocytes nor LN cells, was observed. Moreover, in D-galactosamine-sensitized mice, injection of intact BFA (1 microgram/mice) induced 100% lethality, whereas the same dose of F(ab')2 BFA was not toxic. These results demonstrate that F(ab')2 BFA can induce activation of cytotoxic lymphocytes only in the presence of relevant tumor cells, both in vitro and in vivo. That these activated lymphocytes can be redirected to lyse relevant tumor cells by the same BFA has important implications for the clinical application of BFA anti-tumor therapies.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
155
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1296-303
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:7636196-Animals, pubmed-meshheading:7636196-Antibodies, Bispecific, pubmed-meshheading:7636196-Antigens, Neoplasm, pubmed-meshheading:7636196-Cytotoxicity, Immunologic, pubmed-meshheading:7636196-Female, pubmed-meshheading:7636196-Galactosamine, pubmed-meshheading:7636196-Humans, pubmed-meshheading:7636196-Immunoglobulin Fab Fragments, pubmed-meshheading:7636196-Immunotherapy, pubmed-meshheading:7636196-Lymphocyte Activation, pubmed-meshheading:7636196-Lymphocytes, Tumor-Infiltrating, pubmed-meshheading:7636196-Melanoma, Experimental, pubmed-meshheading:7636196-Melanoma-Specific Antigens, pubmed-meshheading:7636196-Mice, pubmed-meshheading:7636196-Mice, Inbred C3H, pubmed-meshheading:7636196-Muromonab-CD3, pubmed-meshheading:7636196-Neoplasm Proteins, pubmed-meshheading:7636196-Neoplasm Transplantation, pubmed-meshheading:7636196-Receptor-CD3 Complex, Antigen, T-Cell
pubmed:year
1995
pubmed:articleTitle
Anti-CD3 x anti-tumor F(ab')2 bifunctional antibody activates and retargets tumor-infiltrating lymphocytes.
pubmed:affiliation
Department of Surgery, Mayo Clinic and Foundation, Rochester, MN 55905, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't