An intra-patient placebo-controlled phase I trial to evaluate the safety and tolerability of intradermal IMM-101 in melanoma

Stebbing, Justin; Dalgleish, Angus; Gifford-Moore, A.; Martín, Andrés J. Muñoz; Gleeson, Carole D.; Wilson, Georgia; Brunet, Laura Rosa; Grange, John M.; Mudan, Satvinder

doi:10.1093/annonc/mdr363

Cited by 41 publications

(37 citation statements)

References 32 publications

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“…One of these, IMM101 (Mycobacterium obuense), was selected for ease of manufacture and similarity to M. vaccae. An early melanoma study [47] showed it was as effective as the early M. vaccae studies, with complete responses being seen in patients with small volume disease in the skin and lung. The overall survival in this cohort of patients was also similar to previous patients on M. vaccae where a 23% 5year survival was shown for patients who were predominantly grade IVc [48].…”

Section: Review Dalgleishmentioning

confidence: 99%

Rationale for Combining Immunotherapy with Chemotherapy

Dalgleish¹

2015

Immunotherapy

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Immunotherapy has usually been considered as an alternative to more traditional modalities. Moreover, it has previously been felt that chemotherapy is inherently immunosuppressive and not suitable for combining with immunotherapy. In this review, the concept of combining different modalities that result in cell death, such as radiotherapy and chemotherapy, with immunotherapy is explored. Tumors actively cause immune suppression which can be reversed by their removal but when this is not possible, enhancing the immune response with nonspecific immune stimulation can enhance the response to other modalities, such as radiotherapy and chemotherapy. Additionally, several chemotherapy agents at low doses selectively inhibit regulatory and suppressor cells.

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Section: Review Dalgleishmentioning

confidence: 99%

Rationale for Combining Immunotherapy with Chemotherapy

Dalgleish¹

2015

Immunotherapy

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“…SRL172 has been associated with minimal toxicity, potent immunostimulatory effects and—in some instances—a promising anticancer profile 254 - 256 . These observations prompted for a Phase I clinical study to evaluate IMM-101 in stage III/IV melanoma patients (NCT01308762), which confirmed IMM-101 to be safe and potentially efficient 257 . Today, the clinical benefits of SRL172 are being investigated in a few trials on cancer-unrelated indications (mainly tuberculosis).…”

Section: Othersmentioning

confidence: 99%

Trial Watch

et al. 2012

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Toll-like receptors (TLRs) are prototypic pattern recognition receptors (PRRs) best known for their ability to activate the innate immune system in response to conserved microbial components such as lipopolysaccharide and double-stranded RNA. Accumulating evidence indicates that the function of TLRs is not restricted to the elicitation of innate immune responses against invading pathogens. TLRs have indeed been shown to participate in tissue repair and injury-induced regeneration as well as in adaptive immune responses against cancer. In particular, TLR4 signaling appears to be required for the efficient processing and cross-presentation of cell-associated tumor antigens by dendritic cells, which de facto underlie optimal therapeutic responses to some anticancer drugs. Thus, TLRs constitute prominent therapeutic targets for the activation/intensification of anticancer immune responses. In line with this notion, long-used preparations such as the Coley toxin (a mixture of killed Streptococcus pyogenes and Serratia marcescens bacteria) and the bacillus Calmette-Guérin (BCG, an attenuated strain of Mycobacterium bovis originally developed as a vaccine against tuberculosis), both of which have been associated with consistent anticancer responses, potently activate TLR2 and TLR4 signaling. Today, besides BCG, only one TLR agonist is FDA-approved for therapeutic use in cancer patients: imiquimod. In this Trial Watch, we will briefly present the role of TLRs in innate and cognate immunity and discuss the progress of clinical studies evaluating the safety and efficacy of experimental TLR agonists as immunostimulatory agents for oncological indications.

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“…Similar clinical observations with responses in cutaneous and lung lesions have been reported, as well as a trend to increased survival, which is currently the focus of a long-term follow up study (ClinicalTrials.gov Identifier NCT01559818). 20 IMM-101 is now in phase II trials for pancreatic cancer (ClinicalTrials. gov.…”

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confidence: 99%