Chimeric antigen receptor macrophage therapy for breast tumours mediated by targeting the tumour extracellular matrix

Zhang, Wenlong; Liu, Ling; Su, Huifang; Liu, Qin; Shen, Jie; Dai, Hanren; Zheng, Wei; Lu, Yan; Zhang, Weijie; Bei, Yuncheng; Shen, Pingping

doi:10.1038/s41416-019-0578-3

Cited by 183 publications

(157 citation statements)

References 36 publications

(38 reference statements)

Supporting

Mentioning

156

Contrasting

Order By: Relevance

“…In order to address some of these shortcomings, several groups have published work using genetically engineered monocytes and macrophages for use as anti-tumor therapeutics (107)(108)(109)(110)(111). De Palma and colleagues developed an approach in which the gene for IFNα, which has known anti-tumor function, was lentivirally transduced into CD34 + hematopoietic stem cells under a Tie2-driven promoter system.…”

Section: Chimeric Antigen Receptor Macrophage (Car-m) Cell Therapy Fomentioning

confidence: 99%

Macrophage-Based Approaches for Cancer Immunotherapy

et al. 2021

View full text Add to dashboard Cite

Adoptive cell therapy with genetically modified T cells has generated exciting outcomes in hematologic malignancies, but its application to solid tumors has proven challenging. This gap has spurred the investigation of alternative immune cells as therapeutics. Macrophages are potent immune effector cells whose functional plasticity leads to antitumor as well as protumor function in different settings, and this plasticity has led to notable efforts to deplete or repolarize tumor-associated macrophages. Alternatively, macrophages could be adoptively transferred after ex vivo genetic modification. In this review, we highlight the role of macrophages in solid tumors, the progress made with macrophage-focused immunotherapeutic modalities, and the emergence of chimeric antigen receptor macrophage cell therapy.

show abstract

Section: Chimeric Antigen Receptor Macrophage (Car-m) Cell Therapy Fomentioning

confidence: 99%

Macrophage-Based Approaches for Cancer Immunotherapy

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Several academic laboratories and companies are working on different CAR-expressing macrophage designs to selectively target tumor antigens, such as Her2, and trigger macrophage phagocytosis of cancer cells. 233,234 However, many more studies will be needed to evaluate this therapeutic strategy, as multiple limiting steps, including cell delivery, specificity, survival, effective cancer killing, and toxicity/adverse effects, could potentially prevent CAR-expressing macrophages from moving to the clinic.…”

Section: Siglec1 (Cd169)mentioning

confidence: 99%

Macrophage targeting in cancer

Lopez‐Yrigoyen

Cassetta

Pollard

2020

Annals of the New York Academy of Sciences

167

129

View full text Add to dashboard Cite

Tumorigenesis is not only determined by the intrinsic properties of cancer cells but also by their interactions with components of the tumor microenvironment (TME). Tumor-associated macrophages (TAMs) are among the most abundant immune cells in the TME. During initial stages of tumor development, macrophages can either directly promote antitumor responses by killing tumor cells or indirectly recruit and activate other immune cells. As genetic changes occur within the tumor or T helper 2 (T H 2) cells begin to dominate the TME, TAMs begin to exhibit an immunosuppressive protumor phenotype that promotes tumor progression, metastasis, and resistance to therapy. Thus, targeting TAMs has emerged as a strategy for cancer therapy. To date, TAM targeting strategies have focused on macrophage depletion and inhibition of their recruitment into the TME. However, these strategies have shown limited therapeutic efficacy, although trials are still underway with combination therapies. The fact that macrophages have the potential for antitumor activity has moved the TAM targeting field toward the development of TAM-reprogramming strategies to support this antitumor immune response. Here, we discuss the various roles of TAMs in cancer therapy and their immunosuppressive properties, as well as implications for emerging checkpoint inhibitor-based immunotherapies. We review state-of-the-art TAM-targeting strategies, focusing on current ones at the preclinical and clinical trial stages that aim to reprogram TAMs as an oncological therapy.

show abstract

“…Besides directly targeting tumour cells, macrophages can be transduced with CAR incorporating CD147 endodomain to express matrix metalloproteinase (MMP). This improved capacity to remodel the extracellular matrix (ECM) subsequently promoted T cell infiltration to inhibit tumour growth in breast cancer xenografts [ 75 ]. This would be beneficial for stroma-enriched solid tumours by removing physical barriers for killer cells to access tumour cells and exert cytotoxicity.…”

Section: Macrophagesmentioning

confidence: 99%

Chimeric Antigen Receptor beyond CAR-T Cells

Qin

D’Souza

Neeson

et al. 2021

Cancers

View full text Add to dashboard Cite

Chimeric antigen receptors (CAR) are genetically engineered receptors that can recognise specific antigens and subsequently activate downstream signalling. Human T cells engineered to express a CAR, also known as CAR-T cells, can target a specific tumour antigen on the cell surface to mediate a cytotoxic response against the tumour. CAR-T cell therapy has achieved remarkable success in treating hematologic malignancies, but not in solid tumours. Currently, extensive research is being carried out to make CAR-T cells a therapy for solid tumours. To date, most of the research interest in the field has focused on cytotoxic T lymphocytes as the carrier of CAR products. However, in addition to T cells, the CAR design can be introduced in other immune cells, such as natural killer (NK)/NKT cells, γδ T cells, mucosal-associated invariant T (MAIT) cells, dendritic cells (DC), macrophages, regulatory T cells (Treg), B cells, etc. Some of the CAR-engineered immune cells, such as CAR- γδ T and CAR-NK/NK-T cells, are directly involved in the anti-tumour response, demonstrated in preclinical studies and/or clinical trials. CAR-Tregs showed promising therapeutic potential in treating autoimmune diseases. In particular, B cells engineered with chimeric receptors can be used as a platform for long-term delivery of therapeutic proteins, such as recombinant antibodies or protein replacement, in an antigen-specific manner. CAR technology is one of the most powerful engineering platforms in immunotherapy, especially for the treatment of cancers. In this review, we will discuss the recent application of the CAR design in non-CAR-T cells and future opportunities in immunotherapy.

show abstract

Chimeric antigen receptor macrophage therapy for breast tumours mediated by targeting the tumour extracellular matrix

Cited by 183 publications

References 36 publications

Macrophage-Based Approaches for Cancer Immunotherapy

Macrophage-Based Approaches for Cancer Immunotherapy

Macrophage targeting in cancer

Chimeric Antigen Receptor beyond CAR-T Cells

Contact Info

Product

Resources

About