Involvement of B lymphocytes in the growth inhibition of human pulmonary melanoma metastases in athymic nu/nu mice by an antibody-lymphotoxin fusion protein Journal Article
| Authors: | Reisfeld, R. A.; Gillies, S. D.; Mendelsohn, J.; Varki, N. M.; Becker, J. C. |
| Article Title: | Involvement of B lymphocytes in the growth inhibition of human pulmonary melanoma metastases in athymic nu/nu mice by an antibody-lymphotoxin fusion protein |
| Abstract: | Antibody-cytokine fusion proteins can target biologically active cytokines to various tumor sites, achieving local concentrations sufficient to induce host immune responses leading to tumor elimination. Here, we demonstrate the therapeutic efficacy of a tumor-specific antibody-lymphotoxin fusion protein (ch225-LT) on xenografted pulmonary metastases or human melanoma. In vitro studies indicated a direct cytotoxic effect of such constructs on melanoma cells via the induction of apoptosis, as demonstrated by cell cycle analysis and DNA fragmentation. However, ch225-LT lacked any therapeutic effect in immune deficient C.B17 scid/beige and scid/scid mice, indicating the insufficiency of this direct mechanism in vivo. In contrast, in athymic nu/nu mice, ch225-LT completely inhibited outgrowth of the xenografted tumor. This therapeutic effect was accompanied by infiltrations of CD45+, Mac-1+, and asialo-GM1+ cells into the tumor; B220+ cells were present in the surrounding tissue and the periphery of the tumor. The functional role of asialo-GM1+ cells was confirmed by in vivo depletion studies. Our data indicate that an antibody-lymphotoxin fusion protein effectively inhibits the growth of disseminated melanoma metastases by mechanisms that function in the absence of mature T cells, but require B, NK, and other asialo-GM1+ cells. |
| Keywords: | immunohistochemistry; human cell; cancer growth; nonhuman; t lymphocyte; mouse; animals; mice; animal tissue; cell death; dna damage; cell cycle; cell division; cancer immunotherapy; melanoma; apoptosis; lung neoplasms; animal experiment; animal model; inflammation; cytotoxicity; mice, scid; b lymphocyte; b-lymphocytes; lung metastasis; cytokine; antibodies, monoclonal; species specificity; hybrid protein; recombinant fusion proteins; drug mechanism; mice, nude; cd11b antigen; transplantation, heterologous; natural killer cell; antibody; lymphocyte depletion; cd45 antigen; lymphotoxin; immunotoxins; lymphotoxin-alpha; humans; human; priority journal; article; gangliotetraosylceramide |
| Journal Title: | Cancer Research |
| Volume: | 56 |
| Issue: | 8 |
| ISSN: | 0008-5472 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 1996-04-15 |
| Start Page: | 1707 |
| End Page: | 1712 |
| Language: | English |
| PUBMED: | 8620479 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 22 November 2017 -- Source: Scopus |
