Adoptive immunotherapy for AML with CD123-engager T cells

نویسندگان

  • Challice Bonifant
  • David Torres
  • Nicholos Joseph
  • Carolyn Arber Barth
  • Mireya Velasquez
  • Xiao-Tong Song
  • Michele Redell
  • Stephen Gottschalk
چکیده

Background T cell immunotherapy is one promising approach to improve outcomes for patients with AML; however, infused T cells do not redirect resident T cells to tumors. To overcome this, we have genetically modified T cells to produce a secretable, bispecific T cell engager (ENG-T cells). Consistent synthesis of engagers by T cells should be superior to the direct infusion of the recombinant bispecific antibody, because bispecific proteins typically have short half-lives and do not accumulate at tumor sites. The goal of this project was to generate and characterize T cells expressing CD123-specific engagers and evaluate the feasibility of using transgenic expression of CD20 in combination with rituximab as a suicide gene.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Redirecting Specificity of T cells Using the Sleeping Beauty System to Express Chimeric Antigen Receptors by Mix-and-Matching of VL and VH Domains Targeting CD123+ Tumors

Adoptive immunotherapy infusing T cells with engineered specificity for CD19 expressed on B- cell malignancies is generating enthusiasm to extend this approach to other hematological malignancies, such as acute myelogenous leukemia (AML). CD123, or interleukin 3 receptor alpha, is overexpressed on most AML and some lymphoid malignancies, such as acute lymphocytic leukemia (ALL), and has been an...

متن کامل

Immunotherapy of acute leukemia by chimeric antigen receptor-modified lymphocytes using an improved Sleeping Beauty transposon platform

Chimeric antigen receptor (CAR)-modified T-cell adoptive immunotherapy is a remarkable therapeutic option proven effective in the treatment of hematological malignancies. In order to optimize cell manufacturing, we sought to develop a novel clinical-grade protocol to obtain CAR-modified cytokine-induced killer cells (CIKs) using the Sleeping Beauty (SB) transposon system. Administration of irra...

متن کامل

AntiCD3Fv fused to human interleukin-3 deletion variant redirected T cells against human acute myeloid leukemic stem cells

BACKGROUND Leukemic stem cells (LSCs) are frequently seen as a cause of treatment failure and relapse in patients with acute myeloid leukemia (AML). Thus, successful new therapeutic strategies for the treatment of AML should aim at eradicating LSCs. The identification of targets on the cell surface of LSCs is getting more and more attention. Among these, CD123, also known as the interleukin-3 (...

متن کامل

Alloreactive Natural Killer Cells for the Treatment of Acute Myeloid Leukemia: From Stem Cell Transplantation to Adoptive Immunotherapy

Natural killer (NK) cells express activating and inhibitory receptors, which recognize MHC class-I alleles, termed "Killer cell Immunoglobulin-like Receptors" (KIRs). Preclinical and clinical data from haploidentical T-cell-depleted stem cell transplantation have demonstrated that alloreactive KIR-L mismatched NK cells play a major role as effectors against acute myeloid leukemia (AML). Outside...

متن کامل

Circulating exosomes carrying an immunosuppressive cargo may interfere with adoptive cell therapies in leukemia

Background Adoptive immunotherapy, including transfer of activated NK cells, is currently under active investigation for patients with refractory and relapsed acute myeloid leukemia (AML). However, a highly immunosuppressive microenvironment sustained in part by tumor-derived exosomes, creates a major hurdle for adoptive immunotherapy. We recently reported that exosomes, virussize (30-100nm) me...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:

دوره 3  شماره 

صفحات  -

تاریخ انتشار 2015