Blocking monoclonal antibodies of TIM proteins as orchestrators of anti-tumor immune response

Baghdadi, Muhammad; Takeuchi, Shintaro; Wada, Haruka; Seino, Ken‐ichiro

doi:10.4161/mabs.32107

Cited by 3 publications

(4 citation statements)

References 71 publications

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“…On the whole, TIM-1 today ranks among the critical immune checkpoints which may serve as targets for therapeutic action aimed, inter alia, at the activation of antitumor immune reactions [52][53][54].…”

Section: Kim-1 and Immune Reactionsmentioning

confidence: 99%

Kidney Injury Molecule 1 (KIM-1): a Multifunctional Glycoprotein and Biological Marker (Review)

Karmakova¹,

Сергеева²,

Kanukoev³

et al. 2021

Sovrem Tehnol Med

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KIM-1 (kidney injury molecule 1) is a transmembrane glycoprotein also known as HAVcr-1 and TIM-1 belongs to the T-cell immunoglobulin and mucin domain family (TIM) of proteins. TIM glycoproteins are presented on the immune cells and participate in the regulation of immune reactions. KIM-1 differs from other members of its family in that it is expressed not only by immunocompetent cells but epithelial cells as well. Cellular and humoral effects mediated by KIM-1 are involved in a variety of physiological and pathophysiological processes.Current understanding of the mechanisms determining the participation of KIM-1 in viral invasion, the immune response regulation, adaptive reactions of the kidney epithelium to acute ischemic or toxic injury, in progression of chronic renal diseases, and kidney cancer development have been presented in this review. Data of clinical researches demonstrating the association of KIM-1 with viral diseases and immune disorders have also been analyzed. Potential application of KIM-1 as urinary or serological marker in renal and cardiovascular diseases has been considered.

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Section: Kim-1 and Immune Reactionsmentioning

confidence: 99%

Kidney Injury Molecule 1 (KIM-1): a Multifunctional Glycoprotein and Biological Marker (Review)

Karmakova¹,

Сергеева²,

Kanukoev³

et al. 2021

Sovrem Tehnol Med

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“…TIM3 is generally considered as an inhibitory immune checkpoint that is preferentially expressed on activated T cells and other immune cells. TIM3 interacts with multiple ligands including galectin-9, CEACAM1, PtdSer, HMGB1, and causes exhaustion and apoptosis of antigen-specific Th1 cells and CTLs, which correlates with impaired antitumor immune response ( 23 ). The blockade of TIM3 has exhibited beneficial effects in T cell-based immunotherapies in some preclinical studies ( 24 , 25 ).…”

Section: Discussionmentioning

confidence: 99%

Generation of TIM3 inhibitory single‑domain antibodies to boost the antitumor activity of chimeric antigen receptor T cells

et al. 2021

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Targeting inhibitory immune checkpoint molecules has significantly altered cancer treatment regimens. T cell immunoglobulin and mucin domain 3 (TIM3) is one of the major inhibitory immune checkpoints expressed on T cells. Blocking the engagement of TIM3 and its inhibitory ligand galectin-9 may potentiate the effects of immunotherapy or overcome the adaptive resistance to the therapeutic blockade of programmed cell death protein 1, cytotoxic T-lymphocyte-associated protein 4, B-and T-lymphocyte attenuator and lymphocyte-activation gene 3, amongst others, as each of these immune checkpoints harbors unique properties that set it apart from the rest. Heavy chain variable fragment (VH)-derived single-domain antibodies (sdAbs) represent a class of expanding drug candidates. These sdAbs have unique advantages, including their minimal size in the antibody class, ease of expression, broad scope for modular structure design and re-engineering, and excellent tumor penetration. In the present study, two sdAbs, TIM3-R23 and TIM3-R53, were generated by immunizing rabbits with the recombinant extracellular domain of TIM3 and applying phage display technology. These sdAbs were easily expressed in mammalian cells. The purified sdAbs were able to bind to both recombinant and cell surface TIM3, and blocked it from binding to the ligand galectin-9. In vivo studies demonstrated that TIM3-R53 was able to potentiate the antitumor activity of chimeric antigen receptor T cells that targeted mesothelin. In conclusion, the results of the present study suggested that TIM3-R53 may be a novel and attractive immune checkpoint inhibitor against TIM3, which is worthy of further investigation.

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“…Blocking tumor immune escape and tolerance mechanisms through immune checkpoints is an effective way to enhance antitumor effect. An immune checkpoint inhibitor, especially the mAb-based one, as an immunoregulatory factor, can specifically bind to T cells or tumor cells, thus enhancing the antitumor ability of T cells (6)(7)(8).…”

Section: Nanobodies Targeting Immune Checkpoint Molecules For Tumor Imentioning

confidence: 99%

“…In general, the nanobody library capacity can easily reach 1x10 8 or 1x10 9 , and diversity is greater than 95%. Furthermore, because VHH has only one variable region, specific antibodies can be screened at 1x10 6 . However, in ordinary antibody Fab or ScFv libraries, the library needs to be large enough to more easily screen for antibodies (93,96,97,102,103).…”

Section: Construction Of Library and Panning Of Nanobodiesmentioning

confidence: 99%

Nanobodies targeting immune checkpoint molecules for tumor immunotherapy and immunoimaging (Review)

et al. 2020

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The immune checkpoint blockade is an effective strategy to enhance the anti-tumor T cell effector activity, thus becoming one of the most promising immunotherapeutic strategies in the history of cancer treatment. Several immune checkpoint inhibitor have been approved by the FDA, such as anti-CTLA-4, anti-PD-1, anti-PD-L1 monoclonal antibodies. Most tumor patients benefitted from these antibodies, but some of the patients did not respond to them. To increase the effectiveness of immunotherapy, including immune checkpoint blockade therapies, miniaturization of antibodies has been introduced. A single-domain antibody, also known as nanobody, is an attractive reagent for immunotherapy and immunoimaging thanks to its unique structural characteristic consisting of a variable region of a single heavy chain antibody. This structure confers to the nanobody a light molecular weight, making it smaller than conventional antibodies, although remaining able to bind to a specific antigen. Therefore, this review summarizes the production of nanobodies targeting immune checkpoint molecules and the application of nanobodies targeting immune checkpoint molecules in immunotherapy and immunoimaging.

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Blocking monoclonal antibodies of TIM proteins as orchestrators of anti-tumor immune response

Cited by 3 publications

References 71 publications

Kidney Injury Molecule 1 (KIM-1): a Multifunctional Glycoprotein and Biological Marker (Review)

Kidney Injury Molecule 1 (KIM-1): a Multifunctional Glycoprotein and Biological Marker (Review)

Generation of TIM3 inhibitory single‑domain antibodies to boost the antitumor activity of chimeric antigen receptor T cells

Nanobodies targeting immune checkpoint molecules for tumor immunotherapy and immunoimaging (Review)

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