Initial phase I/IIa trial results of an autologous tumor lysate, particle-loaded, dendritic cell (TLPLDC) vaccine in patients with solid tumors

Herbert, Garth S.; Vreeland, Timothy J.; Clifton, Guy T.; Greene, Julia M.; Jackson, Doreen O.; Hardin, Mark O.; Hale, Diane F.; Berry, John; Nichol, Pauline; Yin, Sook; Yu, Xianzhong; Wagner, Thomas E.; Peoples, George E.

doi:10.1016/j.vaccine.2018.04.078

Cited by 20 publications

(26 citation statements)

References 18 publications

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“…DAMPs result from the cellular redistribution and/or extracellular release of signals by dying cancer cells that experience endoplasmic reticulum (ER) stress (9–12). Currently, major treatments able to increase DAMPs and thereby to boost T cell response include oncolytic viruses (13), some chemotherapies like anthracyclines (14, 15) but also modalities such as radiotherapy (16, 17), high hydrostatic pressure (18), and photodynamic therapy with various photosensitizers (19, 20). These different ICD inducers actually share the capacity to exert strong pro-oxidant effects leading to protein misfolding which, at some stages, cannot be handled by the unfolded protein response (UPR) (12, 21).…”

Section: Introductionmentioning

confidence: 99%

Low Photosensitizer Dose and Early Radiotherapy Enhance Antitumor Immune Response of Photodynamic Therapy-Based Dendritic Cell Vaccination

et al. 2019

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Recent studies have highlighted the potential of photodynamic therapy (PDT) to induce immunogenic cell death (ICD). The clinical use of photosensitizers (PS) to stimulate an anticancer immune response, and not to sterilize tumor cells, may however require some optimizations. Here, we examined how the dose of PS and the scheduling of PDT influence the generation of danger-associated molecular patterns proteins (DAMPs) and favor T cell antitumor activity. We found that upon photoactivation, a low dose of the non-porphyrinic PS OR141 was more prone than higher doses to induce DAMPs in vitro and to inhibit squamous cell carcinoma growth in mice. We further used PDT-killed cancer cells to prime dendritic cells (DC) and stimulate their maturation to evaluate whether the timing of their injection could influence the antitumor effects of radiotherapy. While PDT-based DC vaccination administered before radiotherapy failed to increase tumor growth inhibition, DC injection in the peri-radiotherapy period led to significant tumor growth delay, emphasizing the importance of the coincidence of T cell activation and alterations of the tumor bed. In conclusion, the use of OR141 as a bona fide ICD inducer led us to unravel both the non-linear relationship between PS concentration and PDT-induced antitumor immune response, and the value of an optimal timing of PDT when co-administered with conventional anticancer therapies. This study therefore stresses the necessity of adapting the clinical use of PDT when the goal is to promote an immune response and identifies PDT-based DC vaccination as a suitable modality to reach such objective.

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Section: Introductionmentioning

confidence: 99%

Low Photosensitizer Dose and Early Radiotherapy Enhance Antitumor Immune Response of Photodynamic Therapy-Based Dendritic Cell Vaccination

et al. 2019

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“…69 Other studies have been performed with similar strategies and also have shown some clinical promise. 71 Along similar lines, cancer vaccines have the same intent as DC therapies in mounting an effective immune response to tumors via priming the immune system. HIF-1a278-287 peptide, a HIF-1a derivative, was shown to be able to induce tumor-reactive T cells that had increased efficacy against RCC cells in the peripheral blood monocytes derived from RCC patients.…”

Section: Immunomodulatorymentioning

confidence: 99%

Potential New Therapeutic Approaches for Renal Cell Carcinoma

Yang

Chen

2020

Seminars in Nephrology

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Renal cell carcinoma (RCC) is increasing in incidence and one third of newly diagnosed cases already are metastatic. The metastatic spread of solid tumors renders RCC incurable by surgical resection and consequently more difficult to treat. New molecular-targeted therapies have played a pivotal role in RCC treatment. Unfortunately, tumors frequently develop resistance to these targeted therapies by activating bypass pathways in which alternative signaling or biochemical pathways are activated in response to targeted inhibition of a signaling pathway, allowing cancer cells to continue to survive. Although the advent of immunotherapy with checkpoint inhibitors has led to significant changes in the treatment landscape for advanced RCC, many issues remain to be resolved. For these reasons, there is an urgent need to develop novel therapies and new treatment paradigms for patients with RCC. Much research has been performed thus far in identifying novel targets and treatment strategies in RCC and many of these currently are under investigation and/or in clinical trials. In this article, we discuss therapeutic options in the management of RCC with a focus on the new therapeutic approaches currently investigated in research and for use in the clinic. We divide these potential novel therapies into five groups: nonbiologics, small-molecule drugs, biologics, immunomodulatory therapies, and peptide drugs. We also present some therapeutics and treatment paradigms.

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“…Despite this, cellular vaccines that utilize an individual patient's tumor lysate loaded onto antigenpresenting dendritic cells to elicit a strong T cell response from patients are also currently being investigated in clinical trials. 32,33 Vaccine manufacturing can be a challenging endeavor, as the final product can suffer from inherent variability in both starting material and assays used to demonstrate quality.…”

Section: Vaccinesmentioning

confidence: 99%

The Confluence of Innovation in Therapeutics and Regulation: Recent CMC Considerations

Gutiérrez

Cauchon

Christian

et al. 2020

Journal of Pharmaceutical Sciences

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The field of human therapeutics has expanded tremendously from small molecules to complex biological modalities, and this trend has accelerated in the last two decades with a greater diversity in the types and applications of novel modalities, accompanied by increasing sophistication in drug delivery technology. These innovations have led to a corresponding increase in the number of therapies seeking regulatory approval, and as the industry continues to evolve regulations will need to adapt to the ever-changing landscape. The growth in this field thus represents a challenge for regulatory authorities as well as for sponsors. This review provides a brief description of novel biologics, including innovative antibody therapeutics, genetic modification technologies, new developments in vaccines, and multifunctional modalities. It also describes a few pertinent drug delivery mechanisms such as nanoparticles, liposomes, coformulation, recombinant human hyaluronidase for subcutaneous delivery, pulmonary delivery, and 3D printing. In addition, it provides an overview of the current CMC regulatory challenges and discusses potential methods of accelerating regulatory mechanisms for more efficient approvals. Finally, we look at the future of biotherapeutics and emphasize the need to bring these modalities to the forefront of patient care from a global perspective as effectively as possible.

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Initial phase I/IIa trial results of an autologous tumor lysate, particle-loaded, dendritic cell (TLPLDC) vaccine in patients with solid tumors

Cited by 20 publications

References 18 publications

Low Photosensitizer Dose and Early Radiotherapy Enhance Antitumor Immune Response of Photodynamic Therapy-Based Dendritic Cell Vaccination

Low Photosensitizer Dose and Early Radiotherapy Enhance Antitumor Immune Response of Photodynamic Therapy-Based Dendritic Cell Vaccination

Potential New Therapeutic Approaches for Renal Cell Carcinoma

The Confluence of Innovation in Therapeutics and Regulation: Recent CMC Considerations

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