Immunotherapy
-
Subcutaneous allergen-specific immunotherapy has long been used in allergic rhinitis and/or asthma and has been recognized to be efficacious. However, owing to the inconvenience of injection and the risk of serious side effects, alternative concepts inspiring the search for effective noninjective routes, namely sublingual administration of allergens, have emerged. Sublingual immunotherapy (SLIT) appears to be associated with a lower incidence of systemic reactions. ⋯ In addition, recent studies have proved similarities of the immunological changes with the treatment of both routes. Further comparative clinical and immunological studies of SLIT versus SCIT are needed to confirm the long-term efficacy and to complete the knowledge of immunological mechanisms of both routes. Moreover, better understanding of the interaction of allergen and oral mucosal dendritic cells during SLIT may allow improved targeting of SLIT vaccines.
-
We have previously shown that immunization with an adenovirus vector carrying an individual antigen induces antigen-specific CD8 T cells actively engaged in the destruction of tumor cells expressing the cognate antigen. In order to expand the range of antitumor responses beyond an individual antigen, we designed a recombinant adenovirus type 5 (rAd5) carrying a fusion construct of two full-length antigens. We used this adenovirus vector to test the concept that multiantigenic effector T cells could be generated simultaneously following a single immunization. ⋯ Immunization of mice with rAd5 vector carrying a fusion construct of PSA and PSCA (Ad5-PSA/PSCA) simultaneously induced the expansion of anti-PSA and anti-PSCA CD8 T cells, as measured by intracellular cytokine staining for IFN-γ. The antigen-specific T-cell responses that developed were efficient in eliminating the target cells expressing cognate antigens measured by an in vivo cytotoxic T-cell assay. The in vivo tumor growth study showed that immunization of mice with Ad5-PSA/PSCA vaccine induced strong antitumor immunity when challenged with mouse prostate tumor cell lines (RM11) expressing human PSA (RM11/PSA). To further analyze the impact on therapeutic efficacy of Ad5-PSA/PSCA vaccine against the tumor cells expressing PSA and PSCA (RM11-PSA/PSCA) antigens, we injected mice with Ad5-PSA/PSCA vaccine. The vaccine inhibited the growth of established tumors with 80% of the mice becoming tumor free. These data provide useful information that antigen-specific effector T cells can be generated simultaneously and that their additive antitumor effect has the potential to eliminate the growth of established tumors. Therefore, the immunotherapy approach of using the simultaneous targeting of dual antigens associated with prostate cancer may have important implications for human clinical trials.
-
Among the treatments available for respiratory allergy, which include allergen avoidance and pharmacotherapy, specific immunotherapy (SIT) is the only treatment able to not only act on the symptoms of allergy but also act on the causes. SIT is the practice of administering gradually increasing doses of the specific causative allergen to reduce the clinical reactivity of allergic subjects and was introduced one century ago. SIT remained an empirical treatment for more than 40 years, but the first controlled trial in 1954 paved the way for the scientific era. ⋯ Current available data give solid evidence to the clinical efficacy of both SCIT and SLIT in allergic rhinitis and asthma. Providing the recommended doses and administration schedules are adhered to, the safety and tolerability are very good; however, adverse systemic reactions remain a drawback for SCIT. After one century of use, accumulating evidence surrounds SIT and the central role in the management of respiratory allergy.
-
Immunotherapeutics have been applied intratumorally to manage accessible lesions and to induce systemic immunity in malignant melanoma. Intratumoral bacillus Calmette-Guérin (BCG) has been used for 40 years, and intratumoral BCG, IL-2, IFN-α and imiquimod are recommended as treatment options for patients with in-transit melanoma metastases. Regression of cutaneous metastases can be achieved. ⋯ There are few controlled trials, and whether survival is impacted with any approach has not yet been established. The immunotherapeutics applied and the intratumoral administration procedure itself can activate responses that are immune inhibitory. More rigorous clinical testing and improved understanding and modulation of regulatory immune responses are necessary.
-
Brentuximab vedotin is a novel antibody-drug conjugate consisting of the anti-CD30 antibody cAC10 chemically conjugated to monomethylauristatin E, a potent antimicrotubule agent. Preliminary response rates of 75% in relapsed/refractory Hodgkin's lymphoma and 87% in relapsed/refractory systemic anaplastic large-cell lymphoma were recently reported in large Phase II trials. ⋯ The impressive response rates and limited toxicity of brentuximab vedotin are very promising for relapsed/refractory patients with few treatment options. In addition, the possibilities for incorporation into front-line therapies for both Hodgkin's lymphoma and systemic anaplastic large-cell lymphoma are intriguing.