Limits...
What is the influence of vaccination's routes on the regression of tumors located at mucosal sites?

Nardelli-Haefliger D, Romero P, Jichlinski P - Oncoimmunology (2012)

Bottom Line: Tumor-regressions following tumor-associated-antigen vaccination in animal models contrast with the limited clinical outcomes in cancer patients.Most animal studies however used subcutaneous-tumor-models and questions arise as whether these are relevant for tumors growing in mucosae; whether specific mucosal-homing instructions are required; and how this may be influenced by the tumor.

View Article: PubMed Central - PubMed

Affiliation: Department of Urology; Centre Hospitalier Universitaire Vaudois; Lausanne, Switzerland.

ABSTRACT
Tumor-regressions following tumor-associated-antigen vaccination in animal models contrast with the limited clinical outcomes in cancer patients. Most animal studies however used subcutaneous-tumor-models and questions arise as whether these are relevant for tumors growing in mucosae; whether specific mucosal-homing instructions are required; and how this may be influenced by the tumor.

No MeSH data available.


Related in: MedlinePlus

Vaccination routes and mucosal tumor regression.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3376991&req=5

Figure 1: Vaccination routes and mucosal tumor regression.

Mentions: Persistent infection by oncogenic types of human papillomavirus (HPV) is the central etiological agent of several ano-genital cancers, including cervical cancer, the second cause of cancer death in women worldwide. Since carcinogenesis requires stable expression of HPV-E6 and -E7 oncogenes, these have been tumor-associated-antigens of choice for immunotherapeutic strategies. Parenterally administered therapeutic vaccines have been under active development during the past twenty years. However, none has shown enough clinical efficacies to reach commercialization. To address the role of immunization routes for inducing tumor-protection in mucosal locations (Fig. 1), we developed a novel orthotopic murine model for cervical cancer.1 We compared parenteral and mucosal immunization routes for their ability to induce E7-specific cytotoxic T lymphocytes (E7-CTL) in the genital mucosa (GM), as well as protection against genital tumors (GT). Our data showed that subcutaneous (s.c.) immunization with an adjuvanted E7 polypeptide was more efficient than intranasal (i.n.) or intravaginal (ivag) routes at inducing systemic responses. The three immunization routes induced however similar numbers of E7-CTL in the GM, suggesting a better homing of these lymphocytes to the GM after i.n. and ivag immunization.2 This is in line with the concept of a common mucosal immune system, where antigen presentation occurring in a mucosal site lead to priming of lymphocytes with a tendency to selectively home to the same or other specific mucosal sites. How far this concept can be applied to the GM has been a matter of controversy with either parenteral or different mucosal immunization routes yielding disparate results with different vaccines and/or readouts.3,4 Superiority or efficacy of mucosal lymphocyte trafficking has however been only assessed for the induction of immune responses after infections and/or immunization or to provide protection against a pathogenic challenge. Whether this may hold true for inducing regression of mucosal tumor was to our knowledge not previously examined.


What is the influence of vaccination's routes on the regression of tumors located at mucosal sites?

Nardelli-Haefliger D, Romero P, Jichlinski P - Oncoimmunology (2012)

Vaccination routes and mucosal tumor regression.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3376991&req=5

Figure 1: Vaccination routes and mucosal tumor regression.
Mentions: Persistent infection by oncogenic types of human papillomavirus (HPV) is the central etiological agent of several ano-genital cancers, including cervical cancer, the second cause of cancer death in women worldwide. Since carcinogenesis requires stable expression of HPV-E6 and -E7 oncogenes, these have been tumor-associated-antigens of choice for immunotherapeutic strategies. Parenterally administered therapeutic vaccines have been under active development during the past twenty years. However, none has shown enough clinical efficacies to reach commercialization. To address the role of immunization routes for inducing tumor-protection in mucosal locations (Fig. 1), we developed a novel orthotopic murine model for cervical cancer.1 We compared parenteral and mucosal immunization routes for their ability to induce E7-specific cytotoxic T lymphocytes (E7-CTL) in the genital mucosa (GM), as well as protection against genital tumors (GT). Our data showed that subcutaneous (s.c.) immunization with an adjuvanted E7 polypeptide was more efficient than intranasal (i.n.) or intravaginal (ivag) routes at inducing systemic responses. The three immunization routes induced however similar numbers of E7-CTL in the GM, suggesting a better homing of these lymphocytes to the GM after i.n. and ivag immunization.2 This is in line with the concept of a common mucosal immune system, where antigen presentation occurring in a mucosal site lead to priming of lymphocytes with a tendency to selectively home to the same or other specific mucosal sites. How far this concept can be applied to the GM has been a matter of controversy with either parenteral or different mucosal immunization routes yielding disparate results with different vaccines and/or readouts.3,4 Superiority or efficacy of mucosal lymphocyte trafficking has however been only assessed for the induction of immune responses after infections and/or immunization or to provide protection against a pathogenic challenge. Whether this may hold true for inducing regression of mucosal tumor was to our knowledge not previously examined.

Bottom Line: Tumor-regressions following tumor-associated-antigen vaccination in animal models contrast with the limited clinical outcomes in cancer patients.Most animal studies however used subcutaneous-tumor-models and questions arise as whether these are relevant for tumors growing in mucosae; whether specific mucosal-homing instructions are required; and how this may be influenced by the tumor.

View Article: PubMed Central - PubMed

Affiliation: Department of Urology; Centre Hospitalier Universitaire Vaudois; Lausanne, Switzerland.

ABSTRACT
Tumor-regressions following tumor-associated-antigen vaccination in animal models contrast with the limited clinical outcomes in cancer patients. Most animal studies however used subcutaneous-tumor-models and questions arise as whether these are relevant for tumors growing in mucosae; whether specific mucosal-homing instructions are required; and how this may be influenced by the tumor.

No MeSH data available.


Related in: MedlinePlus