In the past few years, chimeric antigen receptor (CAR) T-cell therapy has emerged as a promising treatment for cancers that failed standard treatments. Such therapies have already been approved in several blood cancers, such as B-cell leukemia and lymphoma. However, despite this progress, a number of patients relapsed after the treatment, partially due to poor expansion and limited persistence of CAR-T cells in vivo. A significant proportion of patients experienced primary (no response) or secondary (initial response followed by relapse/escape) resistance to CAR T-cell therapy.
Resistance to chimeric antigen receptor (CAR) T cell therapy can be categorized as CAR T cell-dependent and CAR T cell-independent resistance, according to the CAR T cell efficiency, include limited T cell persistence and T cell expansion, caused for example by T cell exhaustion and T cell immunodeficiency, as well as therapy-related toxicity. CAR T cell-independent resistance is due to the antigen loss or retention, and an immunosuppressive tumor microenvironment (TME). Efforts are being made to understand the underlying mechanisms of resistance to CAR T-cell therapy in order to develop alternative strategies that would overcome these limitations. Long-term remission is still uncommon, and most patients relapse. Therefore, there is an urgent need to improve the therapeutic efficacy of CAR-T cells. To overcome these significant challenges, innovative mechanisms hampering CAR T cell-dependent and CAR T cell-independent efficiency is worth exploring. Besides, strategies to engineer more powerful CAR-T cells with improved anti-tumor activity and decreased toxicity are necessary. Furthermore, many areas are still to be explored providing new opportunities for more effective and safer future therapies in hematological malignancies.
In this Research, we would like to discuss new innovations or observations to improve its clinical potential in hematological malignancies and the strategies to overcome limitations of CAR-T cell therapy. We welcome submissions of Original Research Articles, Reviews, and Case reports focusing on the new mechanisms and new engineering strategies. The subtopics covered in this Research Topic are, but are not limited to:
1) New resistance mechanisms that render resistance of hematological malignancies to CAR T-cell killing including T-cell dysfunction, Antigen escape, Immunosuppressive TME, etc
2) Unconventional combinational drug treatment regimen that can enhance insufficient eradication capacity and dysfunction for CAR-T cell treatment
3) New classification system of Risk factors for CAR-T patients could improve efficacy through early intervention and early identification
4) Novel CAR-T platform that has the ability to overcome such resistance, and increase the persistence and expansion of CAR-T cells in hematological malignancies
5) Rare case report on CAR T-cell immunotherapy that helps to explain the underlying mechanism of treatment resistance and provide novel insights into hematological malignancies treatment
In the past few years, chimeric antigen receptor (CAR) T-cell therapy has emerged as a promising treatment for cancers that failed standard treatments. Such therapies have already been approved in several blood cancers, such as B-cell leukemia and lymphoma. However, despite this progress, a number of patients relapsed after the treatment, partially due to poor expansion and limited persistence of CAR-T cells in vivo. A significant proportion of patients experienced primary (no response) or secondary (initial response followed by relapse/escape) resistance to CAR T-cell therapy.
Resistance to chimeric antigen receptor (CAR) T cell therapy can be categorized as CAR T cell-dependent and CAR T cell-independent resistance, according to the CAR T cell efficiency, include limited T cell persistence and T cell expansion, caused for example by T cell exhaustion and T cell immunodeficiency, as well as therapy-related toxicity. CAR T cell-independent resistance is due to the antigen loss or retention, and an immunosuppressive tumor microenvironment (TME). Efforts are being made to understand the underlying mechanisms of resistance to CAR T-cell therapy in order to develop alternative strategies that would overcome these limitations. Long-term remission is still uncommon, and most patients relapse. Therefore, there is an urgent need to improve the therapeutic efficacy of CAR-T cells. To overcome these significant challenges, innovative mechanisms hampering CAR T cell-dependent and CAR T cell-independent efficiency is worth exploring. Besides, strategies to engineer more powerful CAR-T cells with improved anti-tumor activity and decreased toxicity are necessary. Furthermore, many areas are still to be explored providing new opportunities for more effective and safer future therapies in hematological malignancies.
In this Research, we would like to discuss new innovations or observations to improve its clinical potential in hematological malignancies and the strategies to overcome limitations of CAR-T cell therapy. We welcome submissions of Original Research Articles, Reviews, and Case reports focusing on the new mechanisms and new engineering strategies. The subtopics covered in this Research Topic are, but are not limited to:
1) New resistance mechanisms that render resistance of hematological malignancies to CAR T-cell killing including T-cell dysfunction, Antigen escape, Immunosuppressive TME, etc
2) Unconventional combinational drug treatment regimen that can enhance insufficient eradication capacity and dysfunction for CAR-T cell treatment
3) New classification system of Risk factors for CAR-T patients could improve efficacy through early intervention and early identification
4) Novel CAR-T platform that has the ability to overcome such resistance, and increase the persistence and expansion of CAR-T cells in hematological malignancies
5) Rare case report on CAR T-cell immunotherapy that helps to explain the underlying mechanism of treatment resistance and provide novel insights into hematological malignancies treatment
