Trispecific T-cell engagers for dual tumor-targeting of colorectal cancer

Tapia-Galisteo, Antonio; Rodríguez, Íñigo Sánchez; Aguilar-Sopeña, Óscar; Harwood, Seandean L.; Narbona, Javier; Ferreras-Gutiérrez, Mariola; Navarro, Rocío; Martín-García, Laura; Corbacho, Cesáreo; Compte, Marta; Lacadena, Javier; Blanco, Francisco J.; Chames, Patrick; Roda-Navarro, Pedro; Álvarez‐Vallina, Luís; Sanz, Laura

doi:10.1080/2162402x.2022.2034355

Cited by 33 publications

(28 citation statements)

References 49 publications

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“… 82 MsABs are currently under clinical investigation in Phase I–III trials and bear the potential to overcome escape mutations and to access personalized immunotherapy approaches (NCT04631601, NCT03319940, NCT03214666; Table 1 ). 81 , 83 In addition, also cytokines and costimulatory factors involved in T-cell priming and activation can be therapeutically targeted and are under clinical investigations (NCT03307746, NCT03323398, NCT02506153; Table 1 ). 84 …”

Section: Impaired Cancer-immune Cycle Due To Impaired T-cell Priming ...mentioning

confidence: 99%

Immune escape mechanisms and therapeutic approaches in cancer: the cancer-immunity cycle

2022

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The introduction of immune checkpoint inhibitors has changed the therapeutic possibilities for various cancer types. However, despite the success in some entities, a significant fraction of patients does not respond to immune checkpoint inhibitors. A functioning cancer-immunity cycle is needed as the precondition for a clinically meaningful response to immune checkpoint inhibitors. It is assumed that only if each step of the cycle is activated and functioning properly, immune checkpoint inhibitors induce a meaningful immune response. However, an activated cancer-immunity cycle might not be present equally in each patient and cancer type. Ideally, treatment concepts should consider each single step of the cancer-immunity cycle and provide personalized treatment approaches, allowing the adaption to functioning and malfunctioning steps of the individual patient’s specific cancer-immunity cycle. In the following review, we provide an overview of the single steps of the cancer-immunity cycle as well as the impact of malfunctioning steps on the generation of an effective tumor-specific immune response.

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Section: Impaired Cancer-immune Cycle Due To Impaired T-cell Priming ...mentioning

confidence: 99%

Immune escape mechanisms and therapeutic approaches in cancer: the cancer-immunity cycle

2022

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“…scFv and nanobody combinations have also been formulated by flanking anti‐CD3 scFv with anti‐EGFR and anti‐EpCAM nanobodies. The trispecific T‐cell engager induced T cell‐dependent killing of EGFR‐EpCAM double‐positive cells in vitro [ 94 ]. These formats are expected to deliver higher tumor antigen specificity, T cell lysis and fewer adverse effects than the bivalent format.…”

Section: Multi‐specific Formatmentioning

confidence: 99%

Antibody variable region engineering for improving cancer immunotherapy

Lou

Cao

2022

Cancer Communications

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The efficacy and specificity of conventional monoclonal antibody (mAb) drugs in the clinic require further improvement. Currently, the development and application of novel antibody formats for improving cancer immunotherapy have attracted much attention. Variable region‐retaining antibody fragments, such as antigen‐binding fragment (Fab), single‐chain variable fragment (scFv), bispecific antibody, and bi/trispecific cell engagers, are engineered with humanization, multivalent antibody construction, affinity optimization and antibody masking for targeting tumor cells and killer cells to improve antibody‐based therapy potency, efficacy and specificity. In this review, we summarize the application of antibody variable region engineering and discuss the future direction of antibody engineering for improving cancer therapies.

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“…Nanobodies seem particularly suited for the construction of BiTEs and BiKEs because of their better solubility and reformatability (Figure 2B) (2). Several groups have constructed chimeric BiTEs and BiKEs that contain a tumorantigen-specific nanobody fused to an scFv for targeting either CD16 or CD3 (48)(49)(50). Others have constructed BiKEs that contain two nanobodies (51)(52)(53).…”

Section: Nanobody-based Bispecific Killer Cell Engagers (Bikes)mentioning

confidence: 99%

Targeting multiple myeloma with nanobody-based heavy chain antibodies, bispecific killer cell engagers, chimeric antigen receptors, and nanobody-displaying AAV vectors

Hambach

Mann²,

Bannas³

et al. 2022

Front. Immunol.

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Nanobodies are well suited for constructing biologics due to their high solubility. We generated nanobodies directed against CD38, a tumor marker that is overexpressed by multiple myeloma and other hematological malignancies. We then used these CD38-specific nanobodies to construct heavy chain antibodies, bispecific killer cell engagers (BiKEs), chimeric antigen receptor (CAR)-NK cells, and nanobody-displaying AAV vectors. Here we review the utility of these nanobody-based constructs to specifically and effectively target CD38-expressing myeloma cells. The promising results of our preclinical studies warrant further clinical studies to evaluate the potential of these CD38-specific nanobody-based constructs for treatment of multiple myeloma.

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Trispecific T-cell engagers for dual tumor-targeting of colorectal cancer

Cited by 33 publications

References 49 publications

Immune escape mechanisms and therapeutic approaches in cancer: the cancer-immunity cycle

Immune escape mechanisms and therapeutic approaches in cancer: the cancer-immunity cycle

Antibody variable region engineering for improving cancer immunotherapy

Targeting multiple myeloma with nanobody-based heavy chain antibodies, bispecific killer cell engagers, chimeric antigen receptors, and nanobody-displaying AAV vectors

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