Highly active antiretroviral therapy (HAART) improves the immunodeficiency of HIV-infected individuals. In this report we show that HAART increases both naive (CD45RA+CD62L+) and central memory ...(CD45RO+CD62L+) CD4 lymphocytes. On CD8 lymphocytes, HAART induces an increase of naive cells associated with a consistent decrease of effector cells (CD45 RO+CD62L-). No specific differences in phenotypic changes were observed with different HAART regimens, suggesting that, once viral suppression is achieved, the pharmacological class of antiretroviral drugs does not affect immune reconstitution.
Lymph node (LN) is a key tissue in the pathophysiology of mature blood cancers, especially for chronic lymphocytic leukemia (CLL). Within the multiple de-regulated pathways affecting CLL homeostasis, ...the CC-chemokine receptor 7 (CCR7) grants homing of CLL cells into the LN where protective environments foster tumor progression. To cover the lack of specific therapies targeting the CCR7-dependence of CLL to enter into the LN, and aiming to displace the disease from LN, we generated CAP-100, an antibody that specifically binds to hCCR7 and neutralizes its ligand-binding site and signaling. In various in vitro and in vivo preclinical models CAP-100 strongly inhibited CCR7-induced migration, extravasation, homing, and survival in CLL samples. Moreover, it triggered potent tumor cell killing, mediated by host immune mechanisms, and was effective in xenograft models of high-risk disease. Additionally, CAP-100 showed a favorable toxicity profile on relevant hematopoietic subsets. Our results validated CAP-100 as a novel therapeutic tool to prevent the access of CLL cells, and other neoplasia with nodal-dependence, into the LN niches, thus hitting a central hub in the pathogenesis of cancer. The first-in-human clinical trial (NCT04704323), which will evaluate this novel therapeutic approach in CLL patients, is pending.
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