Probiotic-guided CAR-T cells for universal solid tumor targeting

Vincent, Rosa L.; Gurbatri, Candice R.; Redenti, Andrew; Coker, Courtney; Arpaia, Nicholas; Danino, Tal

doi:10.1101/2021.10.10.463366

Cited by 14 publications

(13 citation statements)

References 65 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…98 Vincent et al published a preprint reporting a probioticguided CAR-T cells (ProCARs), in which T cells are engineered to sense synthetic antigens that are produced and released by tumorcolonizing probiotic bacteria. 99 These types of synthetic circuits place normally toxic, or off-target CARs, under temporal and spatial control making previously untenable solutions safe.…”

Section: Tunability and Synthetic Control Of Dominant Immune Regulatorsmentioning

confidence: 99%

“…Additionally, creative use of proximal signaling domains within CAR architectures has led to the development of “LINK” CARs, which signal only in the presence of both “AND” gate antigens 98 . Vincent et al published a preprint reporting a probiotic‐guided CAR‐T cells (ProCARs), in which T cells are engineered to sense synthetic antigens that are produced and released by tumor‐colonizing probiotic bacteria 99 . These types of synthetic circuits place normally toxic, or off‐target CARs, under temporal and spatial control making previously untenable solutions safe.…”

Section: Principle 3: Engineering Solutions With Dominant Effectsmentioning

confidence: 99%

See 1 more Smart Citation

Toward the clinical development of synthetic immunity to cancer

Garcia

Burnett

Roybal

2023

Immunological Reviews

View full text Add to dashboard Cite

SummarySynthetic biology (synbio) tools, such as chimeric antigen receptors (CARs), have been designed to target, activate, and improve immune cell responses to tumors. These therapies have demonstrated an ability to cure patients with blood cancers. However, there are significant challenges to designing, testing, and efficiently translating these complex cell therapies for patients who do not respond or have immune refractory solid tumors. The rapid progress of synbio tools for cell therapy, particularly for cancer immunotherapy, is encouraging but our development process should be tailored to increase translational success. Particularly, next‐generation cell therapies should be rooted in basic immunology, tested in more predictive preclinical models, engineered for potency with the right balance of safety, educated by clinical findings, and multi‐faceted to combat a range of suppressive mechanisms. Here, we lay out five principles for engineering future cell therapies to increase the probability of clinical impact, and in the context of these principles, we provide an overview of the current state of synbio cell therapy design for cancer. Although these principles are anchored in engineering immune cells for cancer therapy, we posit that they can help guide translational synbio research for broad impact in other disease indications with high unmet need.

show abstract

Section: Tunability and Synthetic Control Of Dominant Immune Regulatorsmentioning

confidence: 99%

Section: Principle 3: Engineering Solutions With Dominant Effectsmentioning

confidence: 99%

Toward the clinical development of synthetic immunity to cancer

Garcia

Burnett

Roybal

2023

Immunological Reviews

View full text Add to dashboard Cite

show abstract

“…Therefore, researchers attempted to use engineered bacteria carrying spe-cific "goods" as intra-tumor bioreactors. Vincent et al [59] developed a platform of probiotic-guided CAR-T cells, in which tumor-colonizing probiotics release synthetic targets to label tumor tissue for CAR-mediated lysis in situ. Although this study confirms the safety of engineered bacteria in mouse models, it still has a long way to be applied in clinics.…”

Section: Combination With Car-t Cellsmentioning

confidence: 99%

Current advances in bacteria‐based cancer immunotherapy

Guo,

Liu,

Zhang

2023

Eur J Immunol

View full text Add to dashboard Cite

As the understanding of the tumor microenvironment has deepened, immunotherapy has become a promising strategy for cancer treatment. In contrast to traditional therapies, immunotherapy is more precise and induces fewer adverse effects. In this field, some bacteria have attracted increased attention because of their natural ability to preferentially colonize and proliferate inside tumor sites and exert antitumor effects. Moreover, bacterial components may activate innate and adaptive immunity to resist tumor progression. However, the application of bacteria‐based cancer immunotherapy is hampered by potential infection‐associated toxicity and unpredictable behavior in vivo. Owing to modern developments in genetic engineering, bacteria can be modified to weaken their toxicity and enhance their ability to eliminate tumor cells or activate the antitumor immune response. This review summarizes the roles of bacteria in the tumor microenvironment, current strategies for bacterial engineering, and the synergistic efficiency of bacteria with other immunotherapies. In addition, the prospects and challenges of the clinical translation of engineered bacteria are summarized.

show abstract

“…For instance, bacteria can be engineered to colonize tumors, 133 thereby increasing their local concentration and delivering in situ cytotoxic payloads directly to eliminate tumor cells 134 . In addition to their inherent capacity to stimulate the immune system, bacteria can be designed to enhance the recruitment of T cells to the tumor through chemokine secretion 135 or antigen delivery, inducing antitumor responses in both endogenous 136 and engineered T cells 137 …”

Section: Future Directions For Immune Cell Engineeringmentioning

confidence: 99%

“…134 In addition to their inherent capacity to stimulate the immune system, bacteria can be designed to enhance the recruitment of T cells to the tumor through chemokine secretion 135 or antigen delivery, inducing antitumor responses in both endogenous 136 and engineered T cells. 137 However, there are still significant challenges associated with engineering multicellular circuits that involve bacteria and immune cells. In addition to the clear need to mitigate off-tumor toxicity, 138 current engineered bacteria are usually designed as an autonomous system functioning under quorum sensing 139 with limited feedback from the immune and tumor environment.…”

Section: Engineering Non-immune Cells For Multicellular Circuitsmentioning

confidence: 99%

A synthetic biology approach to engineering circuits in immune cells

Hoces

Miguens‐Blanco

Hernández-López

2023

Immunological Reviews

View full text Add to dashboard Cite

SummaryA synthetic circuit in a biological system involves the designed assembly of genetic elements, biomolecules, or cells to create a defined function. These circuits are central in synthetic biology, enabling the reprogramming of cellular behavior and the engineering of cells with customized responses. In cancer therapeutics, engineering T cells with circuits have the potential to overcome the challenges of current approaches, for example, by allowing specific recognition and killing of cancer cells. Recent advances also facilitate engineering integrated circuits for the controlled release of therapeutic molecules at specified locations, for example, in a solid tumor. In this review, we discuss recent strategies and applications of synthetic receptor circuits aimed at enhancing immune cell functions for cancer immunotherapy. We begin by introducing the concept of circuits in networks at the molecular and cellular scales and provide an analysis of the development and implementation of several synthetic circuits in T cells that have the goal to overcome current challenges in cancer immunotherapy. These include specific targeting of cancer cells, increased T‐cell proliferation, and persistence in the tumor microenvironment. By harnessing the power of synthetic biology, and the characteristics of certain circuit architectures, it is now possible to engineer a new generation of immune cells that recognize cancer cells, while minimizing off‐target toxicities. We specifically discuss T‐cell circuits for antigen density sensing. These circuits allow targeting of solid tumors that share antigens with normal tissues. Additionally, we explore designs for synthetic circuits that could control T‐cell differentiation or T‐cell fate as well as the concept of synthetic multicellular circuits that leverage cellular communication and division of labor to achieve improved therapeutic efficacy. As our understanding of cell biology expands and novel tools for genome, protein, and cell engineering are developed, we anticipate further innovative approaches to emerge in the design and engineering of circuits in immune cells.

show abstract

Probiotic-guided CAR-T cells for universal solid tumor targeting

Cited by 14 publications

References 65 publications

Toward the clinical development of synthetic immunity to cancer

Toward the clinical development of synthetic immunity to cancer

Current advances in bacteria‐based cancer immunotherapy

A synthetic biology approach to engineering circuits in immune cells

Contact Info

Product

Resources

About