Our groundbreaking approach of using Posttransplantation Cyclophosphamide (PTCy) has set a new global standard for graft versus host disease prevention in allogeneic bone marrow transplantation (alloHSCT) and saved many lives. PTCy allows transplantation from mismatched donors, so the donor can be expanded and there are potential donors for each patient. The focus is now on disease relapse, the main cause of death after alloHSCT. The new donor immune system fights cancer, but it becomes disabled as cancer progresses. The identification of populations of tumor cells and the mechanisms that drive disease relapse post-transplant is important to develop new treatment and prevention therapies. We...

Read More

Our groundbreaking approach of using Posttransplantation Cyclophosphamide (PTCy) has set a new global standard for graft versus host disease prevention in allogeneic bone marrow transplantation (alloHSCT) and saved many lives. PTCy allows transplantation from mismatched donors, so the donor can be expanded and there are potential donors for each patient. The focus is now on disease relapse, the main cause of death after alloHSCT. The new donor immune system fights cancer, but it becomes disabled as cancer progresses. The identification of populations of tumor cells and the mechanisms that drive disease relapse post-transplant is important to develop new treatment and prevention therapies. We hypothesize that the bone marrow microenvironment is critical for understanding immune?tumor cell interactions and an ideal source for tailored immune cell therapy known as marrow-infiltrating lymphocytes (MILs) after alloHSCT. This proposal aims to offer state-of-the-art research and its translation into early clinical trials. Aim 1: Investigate effector T cell dynamics and fate in relation to acute myeloid leukemia remission versus relapse after alloHSCT. The goal is to define T cell populations associated with different outcomes in preclinical models. Aim 2: Target the heme metabolic pathway to prevent the relapse of acute myeloid leukemia, exploring its. The role of heme pathway in stemness, immune evasion and metabolic adaptation of relapsed leukemia, and ways to change it or modulate it will be examined. Aim 3: Develop strategies to optimally engineer MILs and conduct innovative trials using MILs as personalized, disease-specific immune therapy. This proposal integrates human studies, animal models, cutting-edge techniques, and tailored cell-based therapies, all poised to have high scientific impact, increased collaborations, and promotion of delivery of innovative and personalized care to patients with cancer at Baylor College of Medicine and throughout Texas.

Read Less