Trial Watch: Monoclonal antibodies in cancer therapy

Galluzzi, Lorenzo; Vacchelli, Erika; Fridman, Wolf H.; Galon, Jérôme; Sautès-Fridman, Catheriné; Tartour, Éric; Zucman‐Rossi, Jessica; Zitvogel, Laurence; Kroemer, Guido

doi:10.4161/onci.1.1.17938

Cited by 108 publications

(85 citation statements)

References 131 publications

(131 reference statements)

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“…Various studies have reported a negative prognostic value for tumor infiltration by Tregs, yet this seems to be strongly influenced by other clinical and biological parameters including tumor type, location, stage as well as the presence or not of other immune effector cells, notably CD8 + cytotoxic T lymphocytes (CTLs). Nowadays, an intense wave of investigation focuses on the development of novel strategies that combine Treg inhibitors with various immunostimulatory agents for the immunotherapy of various neoplasms [4,5].…”

Section: Introductionmentioning

confidence: 99%

Tumor-Infiltrating Regulatory T Cells: Phenotype, Role, Mechanism of Expansion In Situ and Clinical Significance

Tanchot

Terme

Péré

et al. 2012

Cancer Microenvironment

112

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In immunocompetent individuals, the immune system initially eradicates potentially tumorigenic cells as they develop, a capacity that is progressively lost when malignant cells acquire alterations that sustain immunosubversion and/or immunoevasion. One of the major mechanisms whereby cancer cells block antitumor immune responses involves a specific class of immunosuppressive T cells that-in the vast majority of cases-express the Forkhead box P3 (FOXP3) transcription factor. Such FOXP3 + regulatory T cells (Tregs) accumulate within neoplastic lesions as a result of several distinct mechanisms, including increased infiltration, local expansion, survival advantage and in situ development from conventional CD4 + cells.

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Section: Introductionmentioning

confidence: 99%

Tumor-Infiltrating Regulatory T Cells: Phenotype, Role, Mechanism of Expansion In Situ and Clinical Significance

Tanchot

Terme

Péré

et al. 2012

Cancer Microenvironment

112

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“…Adverse events were common, but never serious. NCT01322815, a Phase II study assessing the therapeutic profile of a peptide-based vaccine targeting mutant KRAS combined with standard chemotherapy or a mAb specific for vascular endothelial growth factor A (VEGFA) 259 in patients with colorectal carcinoma, has been terminated owing to poor accrual rate. Four months after the initiation of treatment, 50% of patients were alive and free of progression, but 2 patients receiving GI-4000 plus chemotherapy suffered from serious adverse effects.…”

Section: Ongoing Clinical Trialsmentioning

confidence: 99%

Trial watch: Peptide-based vaccines in anticancer therapy

et al. 2018

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Peptide-based anticancer vaccination aims at stimulating an immune response against one or multiple tumor-associated antigens (TAAs) following immunization with purified, recombinant or synthetically engineered epitopes. Despite high expectations, the peptide-based vaccines that have been explored in the clinic so far had limited therapeutic activity, largely due to cancer cell-intrinsic alterations that minimize antigenicity and/or changes in the tumor microenvironment that foster immunosuppression. Several strategies have been developed to overcome such limitations, including the use of immunostimulatory adjuvants, the co-treatment with cytotoxic anticancer therapies that enable the coordinated release of damage-associated molecular patterns, and the concomitant blockade of immune checkpoints. Personalized peptide-based vaccines are also being explored for therapeutic activity in the clinic. Here, we review recent preclinical and clinical progress in the use of peptide-based vaccines as anticancer therapeutics.Abbreviations: CMP: carbohydrate-mimetic peptide; CMV: cytomegalovirus; DC: dendritic cell; FDA: Food and Drug Administration; HPV: human papillomavirus; MDS: myelodysplastic syndrome; MHP: melanoma helper vaccine; NSCLC: non-small cell lung carcinoma; ODD: orphan drug designation; PPV: personalized peptide vaccination; SLP: synthetic long peptide; TAA: tumor-associated antigen; TNA: tumor neoantigen

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“…237,[255][256][257][258] Perhaps the most successful (immuno)therapeutic paradigm of this type is represented by socalled immune checkpoint blockers, i.e., molecules that inhibit the delivery of immunosuppressive signals to activated T lymphocytes and other immune effector cells. 74,75,[259][260][261][262] Besides exerting clinical activity as standalone interventions against various neoplasms, these agents, including the FDA-approved monoclonal antibodies ipilimumab, which targets cytotoxic T lymphocyte-associated protein 4 (CTLA4), [207][208][209][210][211][212] and pembrolizumab (also known as Keytruda TM ), which targets PD-1, [263][264][265] significantly improve the antineoplastic profile of many immunotherapeutics, [266][267][268] including peptide-based anticancer vaccines. 100,113 Large, randomized clinical studies are urgently awaited to identify the combinatorial immunotherapeutic regimens that are best suited to boost the antineoplastic activity of recombinant/purified TAAs and peptides thereof.…”

Section: Discussionmentioning

confidence: 99%

“…Nowadays, great interest is attracted by combinatorial regimens involving other immunostimulatory interventions, 67 including (but not limited to) immunogenic chemotherapeutics, [68][69][70][71] radiotherapy, 72,73 and immune checkpoint blockers. 74,75 Importantly, immune responses against antigens that are not directly targeted by the original vaccine formulation can also develop as a consequence of "epitope spreading". [76][77][78][79][80] Epitope spreading may occur as cancer cells succumbing to vaccine-elicited T lymphocytes release potentially antigenic TAAs along with damage-associated molecular patterns, which deliver potent immunostimulatory signals.…”

Section: Introductionmentioning

confidence: 99%