Development of Ipilimumab: Contribution to a New Paradigm for Cancer Immunotherapy

Hoos, Axel; Ibrahim, Ramy; Korman, Alan J.; Abdallah, Kald; Berman, David M.; Shahabi, Vafa; Chin, Kevin M.; Canetta, Renzo; Humphrey, Rachel

doi:10.1053/j.seminoncol.2010.09.015

Cited by 221 publications

(177 citation statements)

References 67 publications

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“…Higher rates of spontaneous cancer development have been observed in mice with deficient immune systems (2). In humans, the role of T cells in the elimination of tumors has been highlighted by the considerable success of mAb treatments that interfere with T-cell checkpoints (checkpoint inhibitors) and chimeric antigen receptor therapy (3,4,5,6). The immune response can thus serve as a barrier to cancer.…”

Section: Introductionmentioning

confidence: 99%

Innate Lymphoid Cells in Cancer

Vallentin

Barlogis

Pipéroglou

et al. 2015

Cancer Immunology Research

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The world of lymphocytes has recently expanded. A group of cells, innate lymphoid cells (ILC), has been defined. It includes lymphoid cells that have been known for decades, such as natural killer (NK) cells and lymphoid tissue-inducer (LTi) cells. NK cells recognize a vast array of tumor cells, which they help to eliminate through cytotoxicity and the production of cytokines, such as IFNg. Advances in our understanding of NK-cell biology have led to a growing interest in the clinical manipulation of these cells in cancer. The other ILCs are found mostly in the mucosae and mucosal-associated lymphoid tissues, where they rapidly initiate immune responses to pathogens without the need for specific sensitization. Here, we outline the basic features of ILCs and review the role of ILCs other than NK cells in cancer. Much of the role of these ILCs in cancer remains unknown, but several findings should lead to further efforts to dissect the contribution of different ILC subsets to the promotion, maintenance, or elimination of tumors at various anatomic sites. This will require the development of standardized reagents and protocols for monitoring the presence and function of ILCs in human blood and tissue samples.

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Section: Introductionmentioning

confidence: 99%

Innate Lymphoid Cells in Cancer

Vallentin

Barlogis

Pipéroglou

et al. 2015

Cancer Immunology Research

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“…1,2 These agents showed durable clinical benefit and increased OS, 3,4 for patients with advanced melanoma. Since then, the usage of anti-CTLA-4 mAbs (either ipilimumab, IPI or tremelimumab) in several clinical studies or in the context of expanded access programs (EAP) has shown significant increase in OS for MM patients, and promising clinical activity for tumors with other histology.…”

Section: Introductionmentioning

confidence: 99%

Immunological markers and clinical outcome of advanced melanoma patients receiving ipilimumab plus fotemustine in the NIBIT-M1 study

Maccalli

Giannarelli²,

Capocefalo³

et al. 2015

OncoImmunology

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Moreover, either the absence or the presence of soluble NKG2D ligands (ULBP-1 or ¡2) at baseline in the serum of MM patients enabled to discriminate subjects with long-term survival (median overall survival, (OS) D 33.6 mo for ULBP-1 and ¡2) from poor survivors (OS D 9.8 or 6.6 mo, respectively). Conversely, no significant association between the levels of soluble MICA, MICB and ULBP-3 and the clinical outcome of patients was observed. An inverse correlation between circulating levels of these molecules at baseline and frequency of either CD3 C CD4 C CD45RO C BTLA C or Th17 or CD3 C CD4 C 4-1BB C T cells occurred in patients with a favorable clinical outcome. The simultaneous monitoring of different immune parameters, though validation in a large cohort of patients is needed, allowed to identify an association between phenotypic and soluble markers representing a possible predictive immunological signature for the clinical activity of IPI plus FTM.

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“…Поэтому, с целью ингибирования рецептора CTLA-4, был создан иммунотерапевтический препарат ипиллимумаб, кото-рый представляет собой гуманизированные моноклональ-ные комплементсвязывающие антитела (IgG1) к данному рецептору. Предполагалось, что антитела к CTLA-4, пре-пятствуя взаимодействию рецептора c молекулами B7 антигенпрезентирующих клеток, будут способствовать формированию иммунных по отношению к опухоли кло-нов цитотоксических Т-лимфоцитов [19,20]. В настоящее время эта концепция получила широкое распространение.…”

Section: Ctla-4-рецепторunclassified

Lymphoid infiltration as a predictor of successful immunotherapy with melanoma

Titov¹,

Chikileva²,

Киселевский³

et al. 2017

Zlokač. opuholi

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Лимфоидная инфильтрация как предиктор эффективности иммунотерапии меланомыLymphoid infiltration as a predictor of successful immunotherapy with melanoma www.malignanttumours.org • № 1 -2017 г. (22) • MALIGNANT TUMOURS РезюмеМеланома кожи составляет 1-4% от всех онкологических заболеваний. Среди всех злокачественных опухолей кожи меланома занимает особое место, на ее долю приходится около 4% от всех форм онкологических заболеваний кожи, однако 80% смертей в данной группе обусловлено именно меланомой. В 2014 году в России стандартизованный показатель смертности от меланомы кожи составил 1,51 на 100 000 населения. Заболеваемость меланомой кожи в РФ и многих странах мира неуклонно растет. По абсолютному приросту заболеваемости среди всех злокачественных опухолей меланома кожи занимает 2 место после рака легкого. Увеличение числа случаев заболеваемости меланомой диктует необходимость углубленного изучения биологии данной опухоли и ее взаимодействия с системой иммунобиологического надзора. Учитывая иммуногенность меланомы, важное значение имеет характер и степень иммунного ответа на опухоль. Поэтому одним из важных прогностических факторов течения меланомы является степень выраженности и субпопуляционный состав лимфоидной инфильтрации опухоли, которая также имеет значение для подбора индивидуализированного лечения современными иммунотерапевтическими препаратами, в частности ипилимумабом, биомишенью для которого является супрессорный рецептор Т-лимфоцитов CTLA-4. AbstractCutaneous melanoma is 1-4% of all cancers. Among all malignant skin tumors, melanoma has a special place, it accounts for about 4% of all forms of skin cancer, but 80% of deaths in the group of malignant tumors of the skin caused by melanoma. In 2014 in Russian Federation, the standardized death rate from melanoma of the skin was 1.51 per 100 000 population. The incidence of melanoma has been steadily growing in Russian Federation and many other countries. In absolute increase the incidence of all malignant tumors, skin melanoma is ranked 2nd after lung cancer. Increased incidence of melanoma necessitates in-depth study of the biology of this tumor and its interaction with the immunobiological control system. Considering the immunogenicity of melanoma, the importance of the nature of the immune response to growing tumor. Therefore, one of the most important prognostic factor of the disease in these patients is the severity and subpopulations of lymphoid infiltration of the tumor, which is also important for the selection of personalized treatments with modern immunotherapeutic drugs, such as ipilimumab, which is the biological target for T cell suppressor receptor CTLA-4.

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Development of Ipilimumab: Contribution to a New Paradigm for Cancer Immunotherapy

Cited by 221 publications

References 67 publications

Innate Lymphoid Cells in Cancer

Innate Lymphoid Cells in Cancer

Immunological markers and clinical outcome of advanced melanoma patients receiving ipilimumab plus fotemustine in the NIBIT-M1 study

Lymphoid infiltration as a predictor of successful immunotherapy with melanoma

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