Polymorphic Region-Specific Antibody for Evaluation of Affinity-Associated Profile of Chimeric Antigen Receptor.

Antibody applications in cancer immunotherapy involve diverse strategies, some of which redirect T cell-mediated immunity via engineered antibodies. Affinity is a trait that is crucial for these strategies, as optimal affinity reduces unwanted side effects while retaining therapeutic function. Antibody-antigen pairs possessing a broad affinity range are required to define optimal affinity and to investigate the affinity-associated functional profiles of T cell-engaging strategies such as bispecific antibodies and chimeric antigen receptor-engineered T cells. Here, we demonstrate the unique binding characteristic of the developed antibody clone MVR, which exhibits robust binding to B-lymphoid cell lines. Intriguingly, MVR specifically recognizes the highly polymorphic human leukocyte antigen (HLA)-DR complex and exhibits varying affinities that are dependent upon the HLA-DRB1 allele type. Remarkably, MVR binds to the conformational epitope that consists of two hypervariable regions. As an application of MVR, we demonstrate an MVR-engineered chimeric antigen receptor (CAR) that elicits affinity-dependent function in response to a panel of target cell lines that express different HLA-DRB1 alleles. This tool evaluates the effect of affinity on cytotoxic killing, polyfunctionality, and activation-induced cell death of CAR-engineered T cells. Collectively, MVR exhibits huge potential for the evaluation of the affinity-associated profile of T cells that are redirected by engineered antibodies.

Efficacy of Semiannual Single Fixed Low-Dose Rituximab Therapy in Steroid-Dependent Minimal Change Nephrotic Syndrome: A Case Series.

The frequency of using rituximab to treat refractory nephrotic syndrome has recently been increasing, and the conventional dose of rituximab used to treat it, 375 mg/m2 body surface area once weekly for 4 weeks, has been modelled on the chemotherapy regimen for B-cell non-Hodgkin's lymphoma. The dose and intervals of rituximab in refractory nephrotic syndrome remain controversial. Clear lymphoma cell hyperplasia is seen in lymphoma patients, but not in nephrotic syndrome patients. Since we thought that it might be possible to reduce the dose of rituximab if only used for the purpose of depleting CD20-positive B cells in nephrotic patients' peripheral blood, we tried semiannually with a single fixed rituximab dose of 100 mg/body, and a complete remission was attained in 3 cases without treatment with prednisolone or cyclosporine. Our report strongly suggests considering appropriate dose and interval of rituximab therapy in the treatment of steroid-dependent nephrotic syndrome.