Adoptive immune cells therapy (ACT, such as cytokine-induced killer cell, tumor-infiltrating lymphocyte), which mainly focusing on cell harvest and ex vivo expansion, has been developed and evaluated for cancer immunotherapy over tens of years. Unfortunately, the traditional ACT approaches are far from offering curative responses to patients with cancer due to many reasons, among which the efficacy may not be reliable and sustainable. Exactingly, in recently years, modern ACT can imprint a defined and dedicated antigen specificity and exert direct cytotoxic effects against antigen-expressing cancerous cells without antigen-presentation process and MHC independent, including chimeric antigen receptor T cell (CAR-T cell), genetic engineering T-cell receptor T cell (TCR-T cell) and chimeric antigen receptor NK cell (CAR-NK cell). As emergences of synthetic biology, unprecedented and encouraging success has been achieved by CAR-T therapy for hematologic malignancies, illustrating that engineered cytotoxic cells can serve as a powerful new class of cancer therapeutics in the future. However, new strategies how to exert full potential of modern ACT for solid tumors are still appealing because solid tumors always develop complicated obstacles.
Tumor escape from immune surveillance and elimination is a hallmark of cancer, and the existence of different immunosuppressive pathways hinders the utilizing of modern ACT for solid tumor. In general, it can be summarized in 2 ways: (1) to inhibit antitumor activity (mainly acting on T and NK cytotoxic cells), and (2) to induce immunosuppression (acting on cancer-derived macrophages, myeloid-derived-suppressor cells, T regulatory cells and stroma cells). Solid tumors utilize every possible option, including but are not limited to, preventing cytotoxic cell infiltration, attenuating cytotoxic function, inducting inhibiting suppressing cell subtype, promoting cell exhaustion, to prevent from immune attack, et al. So far, intensive laboratory investigations and clinical studies have been performed to act toward different types of target cells and boost antitumor immunity accordingly.
For example, therapeutic blocking immune checkpoint molecules (PD-1, CTLA-4, et al) (ICB) has been proved as one of the most successful immunotherapeutic interventions to date by recovery of anti-tumor T cell response both alone and combination with CAR-T cell therapy. Interestingly, with a focus on solid tumor, some combinational therapy has achieved durable remission and long-term benefit in patients, indicating that ICB is a promising strategy to overcome the current limitations of engineered adoptive cell therapies.
In this topic, we will also discuss the basic research and clinical trials regarding other emerging immune checkpoints blockade (such as Tim-3, CD70, LAG-3, et al) and other hopeful strategies that can reverse immunosuppressive parameters in tumor microenvironment and boost therapeutic functionality of modern ACT targeting solid tumor.
This Research Topic will give a comprehensive overview about the current achievements of combinational therapy (like ICB) in engineered adoptive cell therapies, especially CAR-T, TCR-T and CAR-NK cells, with particular emphasis on the advances of in clinical trials, and gain better insight into this field.
The themes addressed by this research topic will include, but are not limited to, the followings:
• Varies of engineered adoptive cell-based solid tumor immunotherapies and obstacles they are now confronting.
• Basic mechanisms how ICB and other methods would benefits engineered adoptive cell therapies.
• Novel design strategies regarding how to do combinational engineered adoptive cell therapies, both extrinsic and intrinsic.
• Therapeutic advantages in translational research.
• Future directions of combination therapy.
We welcome the submission of Original Research, Reviews, Mini-reviews and Perspective articles.
Manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by robust and relevant validation are considered out of scope of this section. Experimental validations using cell lines only are not acceptable.
Adoptive immune cells therapy (ACT, such as cytokine-induced killer cell, tumor-infiltrating lymphocyte), which mainly focusing on cell harvest and ex vivo expansion, has been developed and evaluated for cancer immunotherapy over tens of years. Unfortunately, the traditional ACT approaches are far from offering curative responses to patients with cancer due to many reasons, among which the efficacy may not be reliable and sustainable. Exactingly, in recently years, modern ACT can imprint a defined and dedicated antigen specificity and exert direct cytotoxic effects against antigen-expressing cancerous cells without antigen-presentation process and MHC independent, including chimeric antigen receptor T cell (CAR-T cell), genetic engineering T-cell receptor T cell (TCR-T cell) and chimeric antigen receptor NK cell (CAR-NK cell). As emergences of synthetic biology, unprecedented and encouraging success has been achieved by CAR-T therapy for hematologic malignancies, illustrating that engineered cytotoxic cells can serve as a powerful new class of cancer therapeutics in the future. However, new strategies how to exert full potential of modern ACT for solid tumors are still appealing because solid tumors always develop complicated obstacles.
Tumor escape from immune surveillance and elimination is a hallmark of cancer, and the existence of different immunosuppressive pathways hinders the utilizing of modern ACT for solid tumor. In general, it can be summarized in 2 ways: (1) to inhibit antitumor activity (mainly acting on T and NK cytotoxic cells), and (2) to induce immunosuppression (acting on cancer-derived macrophages, myeloid-derived-suppressor cells, T regulatory cells and stroma cells). Solid tumors utilize every possible option, including but are not limited to, preventing cytotoxic cell infiltration, attenuating cytotoxic function, inducting inhibiting suppressing cell subtype, promoting cell exhaustion, to prevent from immune attack, et al. So far, intensive laboratory investigations and clinical studies have been performed to act toward different types of target cells and boost antitumor immunity accordingly.
For example, therapeutic blocking immune checkpoint molecules (PD-1, CTLA-4, et al) (ICB) has been proved as one of the most successful immunotherapeutic interventions to date by recovery of anti-tumor T cell response both alone and combination with CAR-T cell therapy. Interestingly, with a focus on solid tumor, some combinational therapy has achieved durable remission and long-term benefit in patients, indicating that ICB is a promising strategy to overcome the current limitations of engineered adoptive cell therapies.
In this topic, we will also discuss the basic research and clinical trials regarding other emerging immune checkpoints blockade (such as Tim-3, CD70, LAG-3, et al) and other hopeful strategies that can reverse immunosuppressive parameters in tumor microenvironment and boost therapeutic functionality of modern ACT targeting solid tumor.
This Research Topic will give a comprehensive overview about the current achievements of combinational therapy (like ICB) in engineered adoptive cell therapies, especially CAR-T, TCR-T and CAR-NK cells, with particular emphasis on the advances of in clinical trials, and gain better insight into this field.
The themes addressed by this research topic will include, but are not limited to, the followings:
• Varies of engineered adoptive cell-based solid tumor immunotherapies and obstacles they are now confronting.
• Basic mechanisms how ICB and other methods would benefits engineered adoptive cell therapies.
• Novel design strategies regarding how to do combinational engineered adoptive cell therapies, both extrinsic and intrinsic.
• Therapeutic advantages in translational research.
• Future directions of combination therapy.
We welcome the submission of Original Research, Reviews, Mini-reviews and Perspective articles.
Manuscripts consisting solely of bioinformatics or computational analysis of public genomic or transcriptomic databases which are not accompanied by robust and relevant validation are considered out of scope of this section. Experimental validations using cell lines only are not acceptable.