A Darwinian perspective on tumor immune evasion

Puleo, Julieann; Polyák, Kornélia

doi:10.1016/j.bbcan.2021.188671

Cited by 7 publications

(4 citation statements)

References 129 publications

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“…Immunotherapies are acknowledged as the best treatment option for (clinically) vulnerable patients, including immunodeficient persons, possibly even when the therapeutic Ab has apparently lost its in vitro efficacy against a new variant [ 73 ], although this view of Wu and colleagues has been criticized [ 74 ]. This motivates to continue the design of multi-epitope multi-antibody immunotherapies as the best guarantee to provide a safe, tolerable, and stable therapeutic candidate in general and more specifically in disease areas, where prevention of evasion from functional Abs is critical for a full recovery, such as tumorigenesis [ 75 ].…”

Section: Discussionmentioning

confidence: 99%

Broad Epitope Coverage of Therapeutic Multi-Antibody Combinations Targeting SARS-CoV-2 Boosts In Vivo Protection and Neutralization Potency to Corner an Immune-Evading Virus

Roodink,

van Erp,

et al. 2024

Biomedicines

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Therapeutic antibodies (Abs) which act on a broader range of epitopes may provide more durable protection against the genetic drift of a target, typical of viruses or tumors. When these Abs exist concurrently on the targeted antigen, several mechanisms of action (MoAs) can be engaged, boosting therapeutic potency. This study selected combinations of four and five Abs with non- or partially overlapping epitopes to the SARS-CoV-2 spike glycoprotein, on or outside the crucial receptor binding domain (RBD), to offer resilience to emerging variants and trigger multiple MoAs. The combinations were derived from a pool of unique-sequence scFv Ab fragments retrieved from two SARS-CoV-2-naïve human phage display libraries. Following recombinant expression to full-length human IgG1 candidates, a biolayer interferometric analysis mapped epitopes to bins and confirmed that up to four Abs from across the bins can exist simultaneously on the spike glycoprotein trimer. Not all the bins of Abs interfered with the spike protein binding to angiotensin converting enzyme 2 (ACE2) in competitive binding assays, nor neutralized the pseudovirus or authentic virus in vitro, but when combined in vivo, their inclusion resulted in a much stronger viral clearance in the lungs of intranasally challenged hamsters, compared to that of those treated with mono ACE2 blockers. In addition, the Ab mixtures activated in vitro reporter cells expressing Fc-gamma receptors (FcγRs) involved in antibody-dependent cellular cytotoxicity (ADCC) and phagocytosis (ADCP). The best four-Ab combination neutralized seventeen variants of concern from Wuhan-Hu1 to Omicron BA.4/BA.5 in vitro.

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Section: Discussionmentioning

confidence: 99%

Broad Epitope Coverage of Therapeutic Multi-Antibody Combinations Targeting SARS-CoV-2 Boosts In Vivo Protection and Neutralization Potency to Corner an Immune-Evading Virus

Roodink,

van Erp,

et al. 2024

Biomedicines

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“…3) Inhibition of tumor killing immune cells and activation of immunosuppressive cells: Regulatory T cells (Tregs) can inhibit the anti-tumor response of T cells. Tregs negatively regulates anti-tumor response in a direct and indirect manner ( Mishra et al, 2021 ; Puleo and Polyak, 2022 ). Curiel et al confirmed that CD4 + CD25+FOXP3+Tregs specifically inhibited anti-tumor T cells in vivo and promoted tumor growth ( Curiel et al, 2004 ).…”

Section: Discussionmentioning

confidence: 99%

Efficacy and safety of PD-1/PD-L1 inhibitors in the treatment of recurrent and refractory ovarian cancer: A systematic review and a meta-analysis

Zeng

Daju

et al. 2023

Front. Pharmacol.

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Objective: To explore the efficacy and safety of PD-1/PD-L1 inhibitors in treating recurrent/refractory ovarian cancer (OC).Methods: The online databases, including PubMed, Embase and Cochrane Library, were searched for relevant literatures on exploring the efficacy and safety of PD-1/PD-L1 inhibitors in the treatment of recurrent/refractory OC. The keywords are as follows: Ovarian neoplasms, programmed death receptor, PD-1, PD-L1, immunotherapy, and immune checkpoint inhibitor. Furthermore, qualified studies were screened for further meta-analysis.Results: In this study, 11 studies (990 patients) were analyzed to evaluate the efficacy of PD-1/PD-L1 inhibitors in the treatment of recurrent/refractory OC. The combined results proved that the objective response rate (ORR) was 6.7%, 95% CI (4.6%,9.2%), disease control rate (DCR) was 37.9%, 95% CI (33.0%, 42.8%), median overall survival (OS) was 10.70 months, 95% CI (9.23, 12.17), and median progression free survival (PFS) was 2.24 months, 95% CI (2.05, 2.43). In addition, in terms of the safety of patients suffering from recurrent/refractory OC and receiving PD-1/PD-L1 inhibitors, the combined treatment related adverse events (TRAEs) were 70.9% (61.7%–80.2%), and the combined immune related adverse events (iAEs) were 29%, 95% CI (14.7%, 43.3%).Conclusion: In patients with recurrent/refractory OC, PD-1/PD-L1 inhibitors were used alone and there was no obvious evidence of improved efficacy and survival. As for safety, the incidences of TRAEs and iAEs are high, so PD1/PD-L1 inhibitors should be applied according to individual conditions.Clinical Trial Registration:https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=367525, identifier CRD42022367525.

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“…One major peculiarity of cancer is its inherent ability to escape immune surveillance. The mechanisms by which tumor cells hijack the immune system are diverse but mostly rely on the cumulative acquisition of genomic changes that lead to a progressive decline of their immunogenicity (1,2). Typical and prominent features of poorly immunogenic tumor cells include (i) low expression of HLA class I molecules and/or co-stimulatory molecules (3,4), (ii) inefficient antigen processing (5-7), (iii) tryptophan depletion (8,9), (iv) upregulation of checkpoint inhibitors (10), (v) increased production of antiinflammatory mediators (11,12) and (vi) resistance to killing by cytotoxic T cells (CTL) (13,14) among others.…”

Section: Introductionmentioning

confidence: 99%

Immunogenic cell death triggered by impaired deubiquitination in multiple myeloma relies on dysregulated type I interferon signaling

Sadiq

Brioli²,

Al-Abdulla³

et al. 2023

Front. Immunol.

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IntroductionProteasome inhibition is first line therapy in multiple myeloma (MM). The immunological potential of cell death triggered by defects of the ubiquitin-proteasome system (UPS) and subsequent perturbations of protein homeostasis is, however, less well defined.MethodsIn this paper, we applied the protein homeostasis disruptors bortezomib (BTZ), ONX0914, RA190 and PR619 to various MM cell lines and primary patient samples to investigate their ability to induce immunogenic cell death (ICD).ResultsOur data show that while BTZ treatment triggers sterile type I interferon (IFN) responses, exposure of the cells to ONX0914 or RA190 was mostly immunologically silent. Interestingly, inhibition of protein de-ubiquitination by PR619 was associated with the acquisition of a strong type I IFN gene signature which relied on key components of the unfolded protein and integrated stress responses including inositol-requiring enzyme 1 (IRE1), protein kinase R (PKR) and general control nonderepressible 2 (GCN2). The immunological relevance of blocking de-ubiquitination in MM was further reflected by the ability of PR619-induced apoptotic cells to facilitate dendritic cell (DC) maturation via type I IFN-dependent mechanisms.ConclusionAltogether, our findings identify de-ubiquitination inhibition as a promising strategy for inducing ICD of MM to expand current available treatments.

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A Darwinian perspective on tumor immune evasion

Cited by 7 publications

References 129 publications

Broad Epitope Coverage of Therapeutic Multi-Antibody Combinations Targeting SARS-CoV-2 Boosts In Vivo Protection and Neutralization Potency to Corner an Immune-Evading Virus

Broad Epitope Coverage of Therapeutic Multi-Antibody Combinations Targeting SARS-CoV-2 Boosts In Vivo Protection and Neutralization Potency to Corner an Immune-Evading Virus

Efficacy and safety of PD-1/PD-L1 inhibitors in the treatment of recurrent and refractory ovarian cancer: A systematic review and a meta-analysis

Immunogenic cell death triggered by impaired deubiquitination in multiple myeloma relies on dysregulated type I interferon signaling

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