Cancer Immunotherapy Targeting the High Molecular Weight Melanoma-Associated Antigen Protein Results in a Broad Antitumor Response and Reduction of Pericytes in the Tumor Vasculature

Maciag, Paulo; Seavey, Matthew M.; Pan, Zhen-Kun; Ferrone, Soldano; Paterson, Yvonne

doi:10.1158/0008-5472.can-08-0287

Cited by 90 publications

(72 citation statements)

References 49 publications

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“…This Listeria-LLO-HMW-MAA vaccine was able to slow the growth of a number of transplanted subcutaneous tumor cells, reduce the appearance of micrometastases in a lung seeding model and slow the appearance of breast tumors in a transgenic mouse model for breast cancer. 69 In addition, the vaccine induced a significant reduction in tumor volume, MVD and pericyte coverage, which correlated with an increase in CD8 T-cell infiltration into the tumor microenvironment. However targeting HMW-MAA did not appear to influence the ability of mice to lay down normal tissue vasculature during pregnancy or wound healing 69 indicating that it had few adverse effects.…”

Section: Ros-mediated Tumor Cell Kill By Listeriamentioning

confidence: 90%

“…69 In addition, the vaccine induced a significant reduction in tumor volume, MVD and pericyte coverage, which correlated with an increase in CD8 T-cell infiltration into the tumor microenvironment. However targeting HMW-MAA did not appear to influence the ability of mice to lay down normal tissue vasculature during pregnancy or wound healing 69 indicating that it had few adverse effects. Taken together these studies suggest that Listeria can break tolerance to ubiquitous self-molecules and destroy tumor vasculature with little consequence to normal vasculature indicating that this may be a promising approach for tumor immunotherapy.…”

Section: Ros-mediated Tumor Cell Kill By Listeriamentioning

confidence: 90%

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Harnessing Listeria monocytogenes to target tumors

Gravekamp

Paterson

2010

Cancer Biology & Therapy

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Section: Ros-mediated Tumor Cell Kill By Listeriamentioning

confidence: 90%

Section: Ros-mediated Tumor Cell Kill By Listeriamentioning

confidence: 90%

Harnessing Listeria monocytogenes to target tumors

Gravekamp

Paterson

2010

Cancer Biology & Therapy

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“…Recently, Maciag et al reported that targeting the pericytes in tumor vasculature can inhibit the growth of tumors (including renal carcinoma) in animal models. 61 In fact, combined therapy targeting both endothelial cells and pericytes has been proposed for clinical trials.…”

Section: Future Targets For Antiangiogenic Therapymentioning

confidence: 99%

Complexity of tumor vasculature in clear cell renal cell carcinoma

Qian

Huang

Wondergem

et al. 2009

Cancer

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Clear cell renal cell carcinoma (CCRCC) is a highly vascularized cancer resistant to conventional chemotherapy and radiotherapy. Antiangiogenic therapy has achieved some effectiveness against this unique malignancy. The complexity of the tumor vasculature in CCRCC has led to differences in correlating tumor microvessel density with patient prognosis. The authors' recent findings demonstrated that there were at least 2 major categories of tumor vessels in CCRCC-namely, undifferentiated and differentiated-correlating with patient prognosis in contrasting ways, with higher undifferentiated vessel density indicating poorer prognosis, and higher differentiated vessel density correlating with better prognosis. Furthermore, the presence of pericytes supporting the differentiated vessels varied in CCRCC. The distributions of pericyte coverage and differentiated vessels in CCRCC were uneven. The tumor margin had a higher pericyte coverage rate for differentiated vessels than did the inner tumor area. The uneven distributions of pericyte coverage and differentiated vessels in CCRCC prompted the authors to revisit the mechanism of tumor central necrosis, which was also known to be a prognostic indicator for CCRCC. The discrepancy of prognostic correlation between protein and messenger RNA levels of vascular endothelial growth factor in CCRCC was discussed. The complexity of the tumor vasculature in CCRCC also led the authors to begin to re-evaluate the therapeutic effects of antiangiogenic agents for each type of tumor vessel, which will in turn significantly broaden understanding of tumor angiogenesis and improve therapeutic effect. Clear cell renal cell carcinoma (CCRCC) is a highly vascularized malignancy. As evaluated by 2-phase multidetector computed tomography angiography, CCRCC is found to be able to develop an aberrant capsular vascular supply with outflow through an ovarian vein or testicular vein, 1 although positron emission tomography shows that blood perfusion of the tumor is reduced compared with normal kidney tissues. 2 Our expression profiling study also indicated that the expression level of vascular endothelial growth factor (VEGF; a potent proangiogenesis factor) in CCRCC is 5-fold higher than in other types of kidney

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“…The reason why Rerum ® could be considered the new Coley's vaccine lays in the consideration that Coley's vaccine was a rudimentary, albeit tremendously efficient, combination of immunotherapy and direct anti-cancer effects that is replicated, in a more controlled and safe manner, by Rerum ® . Thus, each one of the molecules constituting Rerum ® is endowed both with immunomodulating and anti-cancer properties that, in many cases have been known for centuries as it was described for oleic acid, jokingly dubbed "... anti-oncogenes nutraceuticals since the 17th Century" (Maciag et al, 2008). Although the immunomodulating and anti-cancer properties of chondroitin sulfate, vitamin D 3 and oleic acid have been known for, at least, decades, Rerum ® adds a novel feature that is due to the assembly of the three molecules in one single tridimensional supramolecular structure.…”

Section: The Development Of a Novel Approach To Glycosaminoglycan-basmentioning

confidence: 99%

Is Rerum<sup>®</sup> the New Coley's Vaccine?

Ruggiero¹

2017

American Journal of Immunology

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Abstract:In this article I describe the development of an alternative type of immunotherapy that traces its origins to the nineteenth century when Dr. William B. Coley successfully treated inoperable cancer patients with his vaccine. Despite the well-documented successes, the vaccine did not survive Coley's times and was forgotten and neglected for decades in favor of radio-and chemotherapy. In the mid-fifties of the last century, the concept of a therapy based on stimulation of the immune system re-emerged from oblivion even though with a profoundly diverse connotation; the interest in this approach to cancer has grown exponentially ever since, up to the point of appointing immunotherapy of cancer the" breakthrough of the year" in 2013. Most cancer immunotherapies are based on proteins that either empower the immune system or attempt to selectively kill cancer cells. There are, however, some exceptions to this protein-based approach; the pioneering work of Dr. Prudden in New York and our research work in Florence, Italy. Thus, independently of each other, we pursued an alternative concept of immunotherapy that is based on glycosaminoglycans rather than proteins. From this research, a novel, tridimensional supramolecular structure constituted by chondroitin sulfate, vitamin D 3 and oleic acid, designated Rerum ® , was developed with the intent of reviving the historical approach of Dr. Coley at the light of today's knowledge. Here, I describe the rationale for the development of Rerum ® as well as some preliminary results that were presented at

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Cancer Immunotherapy Targeting the High Molecular Weight Melanoma-Associated Antigen Protein Results in a Broad Antitumor Response and Reduction of Pericytes in the Tumor Vasculature

Cited by 90 publications

References 49 publications

Harnessing Listeria monocytogenes to target tumors

Harnessing Listeria monocytogenes to target tumors

Complexity of tumor vasculature in clear cell renal cell carcinoma

Is Rerum<sup>®</sup> the New Coley's Vaccine?

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Cancer Immunotherapy Targeting the High Molecular Weight Melanoma-Associated Antigen Protein Results in a Broad Antitumor Response and Reduction of Pericytes in the Tumor Vasculature

Cited by 90 publications

References 49 publications

Harnessing Listeria monocytogenes to target tumors

Harnessing Listeria monocytogenes to target tumors

Complexity of tumor vasculature in clear cell renal cell carcinoma

Is Rerum<sup>&reg;</sup> the New Coley&#039;s Vaccine?

Contact Info

Product

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Is Rerum<sup>®</sup> the New Coley's Vaccine?