![]() ©2021 American Association for Cancer Research. Our findings propose beneficial remodeling of the TCR repertoire following transient CD4 + cell depletion and provide novel insight into the antitumor effects of monoclonal anti-CD4 treatment in patients with cancer. Estimates of the current size of the human antibody nave repertoire are also widely debated with numbers anywhere from 10 million members, based on experimentally derived numbers, to in excess of one thousand trillion members or more, based on the different sequences derived from theoretical combinatorial calculations. These results suggested that the clonal replacement of the TCR repertoire induced by transient CD4 + cell depletion was accompanied by the expansion of tumor-reactive T-cell clones that mediated antitumor responses. 1 Altmetric Part of the Results and Problems in Cell Differentiation book series (RESULTS,volume 57) Abstract As in mammals, cartilaginous and teleost fishes possess adaptive immune systems based on antigen recognition by immunoglobulins (Ig), T cell receptors (TCR), and major histocompatibility complex molecules (MHC) I and MHC II molecules. The greater expansion of CD8 + overlapping clones was commonly observed in the patients who achieved tumor shrinkage. The total frequency of blood-tumor overlapping clones tended to increase in patients receiving a depleting dose of anti-CD4, which was accompanied by the replacement of overlapping clones. Next, we focused on T-cell clones overlapping between the blood and tumor in order to track tumor-associated T-cell clones in the blood. This replacement of the TCR repertoire was associated with the extent of CD4 + T-cell depletion and an increase in CD8 + T-cell count in the blood. Transient depletion of CD4 + cells promoted replacement of T-cell clones among CD4 + and CD8 + T cells in the blood. The humanization of rabbit antibodies, however, has not been reported. To investigate the clonal T-cell responses following transient CD4 + cell depletion in patients with cancer, we conducted a temporal analysis of the T-cell receptor (TCR) repertoire in the first-in-human clinical trial of IT1208, a defucosylated humanized monoclonal anti-CD4. The rabbit antibody repertoire, which in the form of polyclonal antibodies has been used in diagnostic appli-cations for decades, would be an attractive source for the generation of therapeutic human antibodies.
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |