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Augmentation versus inhibition: effects of conjunctional OX-40 receptor monoclonal antibody and IL-2 treatment on adoptive immunotherapy of advanced tumor

, : Augmentation versus inhibition: effects of conjunctional OX-40 receptor monoclonal antibody and IL-2 treatment on adoptive immunotherapy of advanced tumor. Journal of Immunology 167(11): 6669-6677

Therapeutic efficacy of adoptive immunotherapy of malignancies is proportional to the number of effector T cells transferred. Traditionally, exogenous IL-2 treatment has been used to promote the survival and function of transferred cells. Recently, we described the therapeutic effects of in vivo ligation of the costimulatory receptor, OX-40R, on activated T cells during early tumor growth. In this study, we examined the effects of IL-2 and OX-40R mAb on adoptive immunotherapy of advanced tumors. For treatment of 10-day 3-methylcholanthrene 205 pulmonary metastases, systemic transfer of 50 x 10(6) activated tumor-draining lymph node T cells resulted in >99% reduction of metastatic nodules. With either IL-2 or OX-40R mAb conjunctional treatment, only 20 x 10(6) cells were required. Advanced 10-day 3-methylcholanthrene 205 intracranial tumors could be cured by the transfer of 15 x 10(6) L-selectin(low) T cells derived from draining lymph nodes. In this situation, IL-2 administration inhibited therapeutic effects of the transferred cells. By contrast, 5 x 10(6) T cells were sufficient to cure all mice if OX-40R mAb was administrated. Studies on trafficking of systemically transferred T cells revealed that IL-2, but not OX-40R mAb, impeded tumor infiltration by T cells. Tumor regression required participation of both CD4 and CD8 T cells. Because only CD4 T cells expressed OX-40R at cell transfer, direct CD4 T cell activation is possible. Alternatively, OX-40R might be up-regulated on transferred T cells at the tumor site, rendering them reactive to the mAb. Our study suggests OX-40R mAb to be a reagent of choice to augment T cell adoptive immunotherapy in clinical trials.


PMID: 11714839

DOI: 10.4049/jimmunol.167.11.6669

Other references

Jackson D.M., 1976: Some functional effects produced by the direct application of sympathomimetic amines to various parts of the brain and their alteration by anti psychotic agents. Sedvall, Goran, Borje Uvnas And Yngve Zotterman (Ed ) Wenner-Gren Center International Symposium Series, Vol 25 Antipsychotic Drugs: Pharmacodynamics And Pharmacokinetics Stockholm, Sweden, Sept 17-19, 1974 Ix+459p Illus Pergamon Press: Oxford, England; New York, N Y , Usa Isbn 0-08-019688-8 89-95

Thole, E.; Spek, W., 2008: The ESF's EuroBioFund: sustainable research financing? Start with networking!. EuroBioFund was set up by the European Science Foundation in 2006, with financial support from the European Commission to catalyse the development of large scale pan-European life sciences research programmes by engaging those involved in planning...

Berteaud, A.J.; Bottreau, A.M.; Priore, A.; Pautrizel, A.N.; Berlureau, F.; Pautrizel, R., 1971: Attempt at correlation between the evolution of a disease by Trypanosoma equiperdum and the action of a pulsed and modulated electromagnetic wave. Comptes Rendus Hebdomadaires des Seances de L'academie des Sciences. Serie D: Sciences Naturelles 272(7): 1003-1006

Wild, S., 2015: International Myopain Society (IMS) US chapter meeting. Journal of Bodywork and Movement Therapies 19(1): 124-125

Fuhn, I.E.; Vancea, S., 1961: Eidonomische und okologische Untersuchungen an Eremias arguta deserti (Gmelin) aus Rumanien. Vestnik Ceskoslovenske Zoologicke Spolecnosti, 25: 5-11

White, P., 2002: Food security. The distinction between food safety and food security is explained. The Bioterrorism Preparedness Act is discussed. Suggestions are offered for school foodservice professionals on how to promote food security in their programs.

Henriksson, P.; Svenningsen, N.W.; Juhlin, I.; Haeger, K., 1980: Netilmicin in moderate to severe infections in newborns and infants: a study of efficacy, tolerance and pharmacokinetics. 49 newborns and infants were treated with netilmicin for verified or suspected infections. Infection was verified in 23 patients (mean gestational age 32 weeks and mean body weight 2100 g) and clinical cure or marked improvement occurred in 20 of...

Corachan, M.; Valls, M.E.; Gascon, J.; Almeda, J.; Vilana, R., 1994: Hematospermia: a new etiology of clinical interest. Ten Spanish male tourists developed hematospermia and ultrasonographic evidence of involvement of the prostate and/or seminal vesicles after recreational exposure in bodies of fresh water in the Dogon country of Mali. Schistosoma eggs were detecte...

Sakamoto, N.; Ohtsubo, S.; Masaki, T.; Iguchi, A.; Takeshita, M., 2006: Evaluation of a contralateral biopsy specimen in prostate cancer patients with unilateral suspicious lesions. Introduction: In patients with a clinically unilateral palpable and/or visible lesion confined to the prostate on digital rectal examination and transrectal ultrasonography, the findings of biopsy specimens of a clinically unsuspicious lobe do not...

Freedman, E.G., 2008: Coordination of the eyes and head during visual orienting. Changing the direction of the line of sight is essential for the visual exploration of our environment. When the head does not move, re-orientation of the visual axis is accomplished with high velocity, conjugate movements of the eyes known as sac...