Facing challenges with hope:universal immune cells for hematologic malignancies

Many patients have achieved a favorable overall survival rate since allogenic hematopoietic stem cell transplantation(allo-HSCT)has been widely implemented to treat hematologic malignancies.However,graft-versus-host disease(GVHD)and complications of immunosuppressive drugs after allo-HSCT are the main causes of non-relapse mortality and a poor quality of life.In addition,GVHD and infusion-induced toxicity still occur with donor lymphocyte infusions(DLIs)and chimeric antigen receptor(CAR)T-cell therapy.Because of the special immune tolerance characteristics and anti-tumor ability of universal immune cells,universal immune cell therapy may strongly reduce GVHD,while simultaneously reducing tumor burden.Nevertheless,widespread application of universal immune cell therapy is mainly restricted by poor expansion and persistence efficacy.Many strategies have been applied to improve universal immune cell proliferation and persistence efficacy,including the use of universal cell lines,signaling regulation and CAR technology.In this review we have summarized current advances in universal immune cell therapy for hematologic malignancies with a discussion of future perspectives.

Universal chimeric Fcγreceptor T cells with appropriate affinity for IgG1 antibody exhibit optimal antitumor efficacy

Developing universal CARs with improved flexible targeting and controllable activities is urgently needed.While several studies have suggested the potential of CD16a in tandem with monoclonal antibodies to construct universal CAR-T cells,the weak affinity between them is one of the limiting factors for efficacy.Herein,we systematically investigated the impact of Fcγreceptor(FcγR)affinity on CAR-T cells properties by constructing universal CARs using Fcγreceptors with different affinities for IgG1 antibodies,namely CD16a,CD32a,and CD64.We demonstrated that the activities of these universal CAR-T cells on tumor cells could be redirected and regulated by IgG1 antibodies.In xenografted mice,64CAR chimeric Jurkat cells with the highest affinity showed significant antitumor effects in combination with herceptin in the HER2 low expression U251 MG model.However,in the CD20 high expression Raji model,64CAR caused excessive activation of CAR-T cells,which resulted in cytokine release syndrome(CRS)and the decline of antitumor activity,and 32CAR with a moderate affinity brought the best efficacy.Our work extended the knowledge about FcγR-based universal CAR-T cells and suggested that only the FcγRCAR with an appropriate affinity can offer the optimal antitumor advantages of CAR-T cells.

CAR-T cells for cancer immunotherapy

Adoptive immunotherapy expressing synthetic chimeric antigen receptors(CAR)on T cells through in vitro modifications represents a new and innovative strategy in cancer treatment.This new approach enables T cells to recognize and bind tumor antigens via a single-chain variable fragment recognition domain,circumventing the restriction of major histocompatibility complex.This review summarized the structure/design of CAR-T cells and the evolution process this technology went through,displaying the theoretical foundation for CAR-T therapy,the marketed products and the latest preclinical and clinical research progress.Finally,we provided perspectives on this technology’s development and potential future applications,especially for treating hematological malignant and solid tumors.

Kazhdan-Lusztig cells in some weighted Coxeter groups

Let(W,S) be a Coxeter group with S = I■J such that J consists of all universal elements of S and that I generates a finite parabolic subgroup W_I of W with w_0 the longest element of W_I. We describe all the left cells and two-sided cells of the weighted Coxeter group(W,S,L) that have non-empty intersection with W_J,where the weight function L of(W, S) is in one of the following cases:(i) max{L(s) | s ∈J} < min{L(t)|t∈I};(ii) min{L(s)|s ∈J} ≥L(w_0);(iii) there exists some t ∈ I satisfying L(t) < L(s) for any s ∈I-{t} and L takes a constant value L_J on J with L_J in some subintervals of [1, L(w_0)-1]. The results in the case(iii) are obtained under a certain assumption on(W, W_I).

Symposium on Cell Signaling in Cancer, Development and Stem Cells Held at Tsinghua University

A Symposium on Cell Signaling in Cancer, Development and Stem Cells was held at Tsinghua on June 13-16, 2007 The symposium was co-organized by China＇s State Key Lab of Biomembrane and Membrane Biotechnology, the US National Institute of Health, the University of Chicago, and the Beijing Society for Cell Biology.

Variable Universe Fuzzy Control for Battery Equalization

In order to avoid the overcharge and overdischarge damages, and to improve the lifetime of the lithium-ion batteries, it is essential to keep the cell voltages in a battery pack at the same level,i.e., battery equalization. Based on the bi-directional modified Cuk converter, variable universe fuzzy controllers are proposed to adaptively maintain equalizing currents between cells of a serially connected battery pack in varying conditions. The inputs to the fuzzy controller are the voltage differences and the average voltages of adjacent cell pairs. A large voltage difference requires large equalizing current while adjacent cells both with low/high voltages can only stand small discharge/charge currents. Compared with the conventional fuzzy control method, the proposed method differs in that the universe can shrink or expand as the effects of the input changes. This is important as the input may change in a small range. Simulation results demonstrate that the proposed variable universe fuzzy control method has fast equalization speed and good adaptiveness for varying conditions.