Kaposi's Sarcoma Lesion Progression in {BKV}-Tat Transgenic Mice Is Increased by Inflammatory Cytokines and Blocked by Treatment with Anti-Tat Antibodies

Kaposi’s sarcoma (KS) is an angioproliferative tumor showing an increased frequency and ag-gressiveness in HIV-infected subjects (AIDS-KS), due to the combined effects of inflammatory cytokines (IC), angiogenic factors, and the HIV-1 Tat protein. While the introduction of effective combined antiretroviral regimens greatly improved AIDS-KS incidence and course, it continues to be an incurable disease and the development of new rational targeted therapies is warranted. We used the BKV/Tat transgenic mouse model to evaluate the effects of IC and anti-Tat antibod-ies (Abs) treatment on KS-like lesions arising in BKV/Tat mice . We demonstrated here that IC-treatment increases the severity and delays the regression of KS-like lesions arising in BKV/Tat mice. Further, anti-Tat Abs reduced KS-like lesion severity developing in IC-treated mice when anti-Tat Abs were administered at an early-stage of lesion development as compared to more advanced lesions. Early anti-Tat Abs treatment also accelerated KS-like lesion regres-sion and reduced the rate of severe-grade lesions. This effect was more evident in the first weeks after Ab treatment, suggesting that a longer treatment with anti-Tat Abs might be even more ef-fective, particularly if administered just after lesion development. Although preliminary, these results are encouraging, and the approach deserves further studies for the development of an-ti-Tat Ab-based therapies for AIDS-KS. Clinical studies specifically addressing the effect of an-ti-Tat antibodies in treating AIDS-KS are not yet available. Nevertheless, the effectiveness of an-ti-Tat antibodies in controlling HIV/AIDS progression, likely due to the neutralization of extra-cellular Tat activities, is suggested by several cross-sectional and longitudinal clinical studies, indicating that anti-Tat Ab treatment or Tat-based vaccines may be effective to treat AIDS-KS pa-tients or prevent the tumor in individuals at risk.