Current and Emerging Targets in Immunotherapy for Osteosarcoma

Miwa, Shinji; Shirai, Toshiharu; Yamamoto, Norio; Hayashi, Katsuhiro; Takeuchi, Akihiko; Igarashi, Kentaro; Yokogawa, Noriaki

doi:10.1155/2019/7035045

Cited by 81 publications

(88 citation statements)

References 72 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…21 22 Mifamurtide, a liposome-encapsulated immunotherapy that activates pulmonary macrophages, improved the disease-free and overall survival of patients with osteosarcoma lung metastases. 23 By contrast, MoDC vaccines have yielded little to no clinical responsiveness, [24][25][26] while checkpoint blockade with PD-1 or CTLA-4 antibodies led to objective clinical response rates of approximately 5% in osteosarcoma patients. 27 28 These results underscore the critical need to improve therapeutic options for osteosarcoma.…”

Section: Introductionmentioning

confidence: 99%

Vaccine efficacy against primary and metastatic cancer with in vitro-generated CD103⁺conventional dendritic cells

Zhou

Slone

Chrisikos

et al. 2020

J Immunother Cancer

View full text Add to dashboard Cite

BackgroundType 1 conventional dendritic cells (cDC1s) possess efficient antigen presentation and cross-presentation activity, as well as potent T cell priming ability. Tissue-resident cDC1s (CD103+cDC1s in mice, CD141+cDC1s in humans) are linked with improved tumor control, yet the efficacy of immunotherapy using this population is understudied.MethodsWe generated murine CD103+cDC1s in vitro and examined their expression of cDC1-related factors, antigen cross-presentation activity, and accumulation in tumor-draining lymph nodes (TdLNs). The antitumor efficacy of the in vitro-generated CD103+cDC1s was studied in murine melanoma and osteosarcoma models. We evaluated tumor responses on vaccination with CD103+cDC1s, compared these to vaccination with monocyte-derived DCs (MoDCs), tested CD103+cDC1 vaccination with checkpoint blockade, and examined the antimetastatic activity of CD103+cDC1s.ResultsIn vitro-generated CD103+cDC1s produced cDC1-associated factors such as interleukin-12p70 and CXCL10, and demonstrated antigen cross-presentation activity on stimulation with the toll-like receptor 3 agonist polyinosinic:polycytidylic acid (poly I:C). In vitro-generated CD103+cDC1s also migrated to TdLNs following poly I:C treatment and intratumoral delivery. Vaccination with poly I:C-activated and tumor antigen-loaded CD103+cDC1s enhanced tumor infiltration of tumor antigen-specific and interferon-γ+CD8+T cells, and suppressed melanoma and osteosarcoma growth. CD103+cDC1s showed superior antitumor efficacy compared with MoDC vaccination, and led to complete regression of 100% of osteosarcoma tumors in combination with CTLA-4 antibody-mediated checkpoint blockade. In vitro-generated CD103+cDC1s effectively protected mice from pulmonary melanoma and osteosarcoma metastases.ConclusionsOur data indicate an in vitro-generated CD103+cDC1 vaccine elicits systemic and long-lasting tumor-specific T cell-mediated cytotoxicity, which restrains primary and metastatic tumor growth. The CD103+cDC1 vaccine was superior to MoDCs and enhanced response to immune checkpoint blockade. These results indicate the potential for new immunotherapies based on use of cDC1s alone or in combination with checkpoint blockade.

show abstract

Section: Introductionmentioning

confidence: 99%

Vaccine efficacy against primary and metastatic cancer with in vitro-generated CD103⁺conventional dendritic cells

Zhou

Slone

Chrisikos

et al. 2020

J Immunother Cancer

View full text Add to dashboard Cite

show abstract

“…Complete surgical resection, preceded and followed by chemotherapy treatment, remains the unique and only partially effective approach for osteosarcoma cure [7]. Although the survival rate in OS patients is gradually increased in the last years in response to the multidrug treatment, more effective therapeutic modalities for OS treatment are absolutely needed [8].…”

Section: Introductionmentioning

confidence: 99%

AdipoRon Affects Cell Cycle Progression and Inhibits Proliferation in Human Osteosarcoma Cells

Sapio

Nigro

Ragone

et al. 2020

Journal of Oncology

View full text Add to dashboard Cite

AdipoRon (AdipoR) is the first synthetic molecule acting as a selective and potent adiponectin receptor agonist. Recently, the possible pharmacological use of AdipoR in different pathological conditions has been addressed. Interestingly, initial evidence suggests that AdipoR may have anticancer properties in different preclinical models, such as pancreatic and ovarian cancer. To our knowledge, so far no research has been directed at determining the impact of AdipoR on osteosarcoma, the most aggressive and metastatic bone malignancy occurring in childhood and adolescence age. Here, we investigate the possible antitumor effects of AdipoR in osteosarcoma cell lines. MTT and cell growth curve assays clearly indicate that AdipoR inhibits, at different extents, proliferation in both U2OS and Saos-2 osteosarcoma cell lines, the latter being more sensitive. Moreover, flow cytometry-based assays point out a significant G0/G1 phase accumulation and a contemporary S phase decrease in response to AdipoR. Consistent with the different sensitivity, a strong subG1 appearance in Saos-2 after 48 and 72 hours of treatment is also observed. The investigation of the molecular mechanisms highlights a common and initial ERK1/2 activation in response to AdipoR in both Saos-2 and U2OS cells. Interestingly, a simultaneous and dramatic downregulation of p70S6K phosphorylation, one of the main targets of mTORC1 pathway, has also been observed in AdipoR-treated Saos-2, but not in U2OS cells. Importantly, a strengthening of AdipoR-induced effects was reported upon everolimus-mediated mTORC1 perturbation in U2OS cells. In conclusion, our findings provide initial evidence of AdipoR as an anticancer molecule differently affecting various signaling pathways involved in cell cycle and cell death in osteosarcoma cells and encourage the design of future studies to further understand its pattern of activities.

show abstract

“…Recently, immunotherapy has been heralded as a breakthrough for the management of diverse liquid and solid tumors, and its ascension as a major therapeutic pillar is underscored by a rapidly increasing number of FDA approved immunebased treatments for cancers that are resistant to conventional modalities. The anticancer activities of immunotherapies can be ascribed to the cooperative effector functions exerted by both the innate and adaptive immune arms, and while immunotherapy is highly effective for certain solid tumors like melanoma, renal cell carcinoma, and others, its promise for benefiting patients diagnosed with metastatic OS remains largely disappointing to date (220)(221)(222)(223). Paradoxically, there is convincing evidence that OS can be recognized by trafficking immunocytes, yet successful exploitation of immunotherapeutic strategies remains elusive.…”

Section: Leveraging the Immune System To Combat Os Metastasesmentioning

confidence: 99%

Understanding and Modeling Metastasis Biology to Improve Therapeutic Strategies for Combating Osteosarcoma Progression

2020

View full text Add to dashboard Cite

Osteosarcoma is a malignant primary tumor of bone, arising from transformed progenitor cells with osteoblastic differentiation and osteoid production. While categorized as a rare tumor, most patients diagnosed with osteosarcoma are adolescents in their second decade of life and underscores the potential for life changing consequences in this vulnerable population. In the setting of localized disease, conventional treatment for osteosarcoma affords a cure rate approaching 70%; however, survival for patients suffering from metastatic disease remain disappointing with only 20% of individuals being alive past 5 years post-diagnosis. In patients with incurable disease, pulmonary metastases remain the leading cause for osteosarcoma-associated mortality; yet identifying new strategies for combating metastatic progression remains at a scientific and clinical impasse, with no significant advancements for the past four decades. While there is resonating clinical urgency for newer and more effective treatment options for managing osteosarcoma metastases, the discovery of druggable targets and development of innovative therapies for inhibiting metastatic progression will require a deeper and more detailed understanding of osteosarcoma metastasis biology. Toward the goal of illuminating the processes involved in cancer metastasis, a convergent science approach inclusive of diverse disciplines spanning the biology and physical science domains can offer novel and synergistic perspectives, inventive, and sophisticated model systems, and disruptive experimental approaches that can accelerate the discovery and characterization of key processes operative during metastatic progression. Through the lens of trans-disciplinary research, the field of comparative oncology is uniquely positioned to advance new discoveries in metastasis biology toward impactful clinical translation through the inclusion of pet dogs diagnosed with metastatic osteosarcoma. Given the spontaneous course of osteosarcoma development in the context of real-time tumor microenvironmental cues and immune mechanisms, pet dogs are distinctively valuable in translational modeling given their faithful recapitulation of metastatic disease

show abstract

Current and Emerging Targets in Immunotherapy for Osteosarcoma

Cited by 81 publications

References 72 publications

Vaccine efficacy against primary and metastatic cancer with in vitro-generated CD103⁺conventional dendritic cells

Vaccine efficacy against primary and metastatic cancer with in vitro-generated CD103⁺conventional dendritic cells

AdipoRon Affects Cell Cycle Progression and Inhibits Proliferation in Human Osteosarcoma Cells

Understanding and Modeling Metastasis Biology to Improve Therapeutic Strategies for Combating Osteosarcoma Progression

Contact Info

Product

Resources

About

Current and Emerging Targets in Immunotherapy for Osteosarcoma

Cited by 81 publications

References 72 publications

Vaccine efficacy against primary and metastatic cancer with in vitro-generated CD103+conventional dendritic cells

Vaccine efficacy against primary and metastatic cancer with in vitro-generated CD103+conventional dendritic cells

AdipoRon Affects Cell Cycle Progression and Inhibits Proliferation in Human Osteosarcoma Cells

Understanding and Modeling Metastasis Biology to Improve Therapeutic Strategies for Combating Osteosarcoma Progression

Contact Info

Product

Resources

About

Vaccine efficacy against primary and metastatic cancer with in vitro-generated CD103⁺conventional dendritic cells

Vaccine efficacy against primary and metastatic cancer with in vitro-generated CD103⁺conventional dendritic cells