Cellular requirements for the monoclonal antibody-mediated eradication of an established solid tumor Journal Article
| Authors: | Dyall, R.; Vasovic, L. V.; Clynes, R. A.; Nikolić-Žugić, J. |
| Article Title: | Cellular requirements for the monoclonal antibody-mediated eradication of an established solid tumor |
| Abstract: | Following subcutaneous implantation, the murine lymphoma E.G7 [a variant of EL-4, transfected with the chicken ovalbumin (OVA) gene] up-regulates the CD4 molecule. We previously showed that the administration of an anti-CD4 monoclonal antibody (mAb) to EG.7-bearing mice leads to a rapid and complete regression of large established tumors. This tumor regression was shown to require both CD8+ cells and functional Fcγ receptors (FcγR), as it failed to occur in mice depleted of CD8 cells, or mice genetically deficient in FcγRI/III (γ(-/-) mice). Using adoptive transfer, we now show that the FcγR+ cells required for this regression are the CD11b+ (phagocytic) cells. Furthermore, experiments using peptide tolerization demonstrated that the critical CD8 CTL population in this model is tumor specific. Analysis of tumors at various stages of regression revealed a massive CD11b+ FcγR+ and a marginal CD8 infiltration. In the presence of the CTL determinant OVA-8 on tumor cells and of the antitumor mAb, this CD8 infiltration became remarkable, and correlated with tumor regression. These results identify the specific cellular effecters essential for the mAb-mediated tumor regression, and suggest that FcγR-activated macrophages induced an expansion of tumor-eliminating CTL in situ. |
| Keywords: | nonhuman; solid tumor; cd8 antigen; cd8-positive t-lymphocytes; lymphocytes, tumor-infiltrating; mouse; animals; mice; mice, knockout; cancer immunotherapy; animal experiment; tumor regression; transfection; monoclonal antibody; antibodies, monoclonal; kinetics; cd11b antigen; cytotoxic t lymphocyte; t-lymphocytes, cytotoxic; lymphoma; hematopoietic stem cells; adoptive transfer; fc receptor; receptors, igg; macrophage; antigens, cd4; antibody; chickens; cancer antibody; ovalbumin; priority journal; article; macrophage-1 antigen; cd8+ cell; fcγr |
| Journal Title: | European Journal of Immunology |
| Volume: | 29 |
| Issue: | 1 |
| ISSN: | 0014-2980 |
| Publisher: | Wiley V C H Verlag Gmbh |
| Date Published: | 1999-01-01 |
| Start Page: | 30 |
| End Page: | 37 |
| Language: | English |
| DOI: | 10.1002/(sici)1521-4141(199901)29:01<30::aid-immu30>3.0.co;2-d |
| PUBMED: | 9933083 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 16 August 2016 -- Source: Scopus |
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