Novel neoadjuvant immunotherapy regimen safety and survival in head and neck squamous cell cancer

Wolf, Gregory T.; Fee, Willard E.; Dolan, Robert W.; Moyer, Jeffrey S.; Kaplan, Michael; Spring, Paul M.; Suen, James Y.; Kenady, Daniel E.; Newman, Jason G.; Carroll, William R.; Gillespie, M. Boyd; Freeman, Scott; Baltzer, Lorraine; Kirkley, Terry D.; Brandwein, Harvey; Hadden, John W.

doi:10.1002/hed.21660

Cited by 48 publications

(54 citation statements)

References 22 publications

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“…[56][57][58] Recent approaches tried to modulate immune response by directly targeting molecules involved in the interactions between cancer and the immune system. In particular, several experimental pieces of evidence have demonstrated that Treg eradication by chemical drugs or specific antibodies is a promising strategy to induce a significant anticancer immune response.…”

Section: Immune Therapy: a New Promising Strategy For Hnscc Treatmentmentioning

confidence: 99%

T-helper and T-regulatory cells modulation in head and neck squamous cell carcinoma

Maggioni

Garavello

2017

OncoImmunology

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Head and neck squamous cell carcinoma (HNSCC) is one of the most diffused cancer types, characterized by a high reoccurrence rate, mainly due to the inability of current therapeutic approaches to completely eradicate cancer cells. HNSCC patients often have defective immune functions, thus allowing cancer immune escape and cancer spreading. Particularly important in driving immune escape during HNSCC progression are T-helper and T-regulatory cells. New insights into their mechanisms of action might support the development of effective and long-lasting immunotherapy.

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Section: Immune Therapy: a New Promising Strategy For Hnscc Treatmentmentioning

confidence: 99%

T-helper and T-regulatory cells modulation in head and neck squamous cell carcinoma

Maggioni

Garavello

2017

OncoImmunology

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“…In all cultures, both CD8þ and CD4þ T cells grew out (CD4/CD8 ratio median 2.45, average 5.1 and range 0. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19]. The composition of T cells was not clearly influenced by the culture conditions (Fig.…”

Section: Hpv-specific T Cells Can Be Isolated From Oropharyngeal Tumomentioning

confidence: 99%

“…13,14 In HNSCC a number of cytokine-, antibody-and vaccinebased immunotherapeutic approaches have been tested or are currently underway. [15][16][17] Recently, clinical success was achieved in the field of the immunotherapy of HPV16-induced (pre-) malignancies of the anogenital region, in particular with therapeutic vaccines. [18][19][20] Similar vaccine approaches are tested for the treatment of p53-overexpressing cancers.…”

mentioning

confidence: 99%

Systemic and local human papillomavirus 16‐specific T‐cell immunity in patients with head and neck cancer

Heusinkveld

Goedemans

Briët

et al. 2011

Intl Journal of Cancer

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Squamous cell carcinomas of the head and neck (HNSCC), in particular those of the oropharynx, can be caused by human papilloma virus Type 16 (HPV16). Whereas these HPV-induced oropharyngeal carcinomas may express the HPV16 E6 and E7 oncoproteins and are associated with better survival, the nonvirally induced HNSCC are associated with overexpression of p53. In this study we assessed the presence of systemic and local T cells reactive against these oncoproteins in HNSCC. An exploratory study on the presence, type and function of HPV16-and/or p53-specific T cells in the blood, tumor and/or metastatic lymph node as measured by several immune assays was performed in an unselected group of 50 patients with HNSCC. Tumor tissue was tested for HPV DNA and the overexpression of p53 protein. Almost all HPV161 tumors were located in the oropharynx. Circulating HPV16-and p53-specific T cells were found in 17/47 and 7/45 tested patients. T cells were isolated from tumor cultures and/or lymph nodes of 20 patients. HPV16-specific T cells were detected in six of eight HPV1 tumors, but in none of the 12 HPV-tumors. Tumor-infiltrating p53-specific T cells were not detected. In depth analysis of the HPV16-specific T-cell response revealed that this response comprised a broad repertoire of CD41 T-helper Type 1 and 2 cells, CD41 regulatory T cells and CD81 T cells reactive to HPV16. The local presence of HPV16-specific T-cell immunity in HPV16-induced HNSCC implicates a role in the antitumor response and support the development of immunotherapy for HNSCC.

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“…Subsequently, a cGMP biologic agent designated IRX-2, in combination with the above-described regimen, was explored under corporate sponsorship in the US. A Phase I clinical trial was opened in 2003 and a multicenter Phase 2 trial was recently completed, and results for both studies published [19, 20]. …”

Section: Introductionmentioning

confidence: 99%

Increased lymphocyte infiltration in patients with head and neck cancer treated with the IRX-2 immunotherapy regimen

Berinstein¹,

Wolf

Naylor³

et al. 2011

Cancer Immunol Immunother

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Twenty-seven subjects with squamous cell cancer of the head and neck received the neoadjuvant IRX-2 immunotherapy regimen prior to surgery in a Phase 2 trial. Pretreatment tumor biopsies were compared with the primary tumor surgical specimens for lymphocyte infiltration, necrosis and fibrosis, using hematoxylin and eosin stain and immunohistochemistry in 25 subjects. Sections were examined by three pathologists. Relative to pretreatment biopsies, increases in lymphocyte infiltration (LI) were seen using H and E or immunohistochemistry. CD3+ CD4+ T cells and CD20+ B cells were primarily found in the peritumoral stroma and CD3+ CD8+ T cells and CD68+ macrophages were mainly intratumoral. LI in the surgical specimens were associated with reductions in the primary tumor size. Improved survival at 5 years was correlated with high overall LI in the tumor specimens. Neoadjuvant IRX-2 immunotherapy regimen may restore immune responsiveness presumably by mobilizing tumor infiltrating effector lymphocytes and macrophages into the tumor.

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Novel neoadjuvant immunotherapy regimen safety and survival in head and neck squamous cell cancer

Cited by 48 publications

References 22 publications

T-helper and T-regulatory cells modulation in head and neck squamous cell carcinoma

T-helper and T-regulatory cells modulation in head and neck squamous cell carcinoma

Systemic and local human papillomavirus 16‐specific T‐cell immunity in patients with head and neck cancer

Increased lymphocyte infiltration in patients with head and neck cancer treated with the IRX-2 immunotherapy regimen

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