Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Dueñas-Gonzalez, A. et al.

Dueñas-Gonzalez, Verastegui, Lopez-Graniel, Gonzalez, Mota, Barrera-Franco, Meneses, Chanona, de la Garza, Chavez-Blanco, Hadden,

A pilot study of perilymphatic leukocyte cytokine mixture (IRX-2) as neoadjuvant treatment for early stage cervical carcinoma.

Clinical and experimental data demonstrate that local cytokines are able to induce tumor regression and in some cases antitumor systemic immune response. IRX-2 is a cell-free mixture of cytokines obtained from unrelated donor lymphocytes with demonstrated ability to induce immune mediated regression of squamous cell carcinomas of head and neck. The objective of this study was to evaluate the antitumor activity and toxicity of IRX-2 in untreated early stage cervical cancer patients. Ten consecutive patients clinically staged IB1, IB2 and IIA were treated with a neoadjuvant immunotherapy regimen that consisted in a single IV dose of cyclophosphamide at 300 mg/m2 on day 1, oral indomethacin or ibuprofen and zinc sulfate were administered from days I to 21 and 10 regional perilymphatic injections of IRX-2 on days 3 to 14. All patients were scheduled for radical hysterectomy on day 21. The clinical and pathological responses, toxicity and survival were evaluated. Clinical response was seen in 50% of patients (three partial responses, two minor responses). Seven patients underwent surgery and pathological tumor reduction associated with tumor fragmentation was found in five cases. Histological studies demonstrated a rather heterogeneous cell type infiltrating pattern in the tumor which included lymphocytes, plasma cells, neutrophils, macrophages and eosinophils. Immunohistochemical analysis of the surgical specimens demonstrated an increase of tumor infiltrating CD8+ cells. The treatment was well tolerated except for mild pain and minor bleeding during injections and gastric intolerance to indomethacin. At 31 months of maximum follow-up (median 29), eight patients are disease-free. Our results suggest that the immunotherapy approach used induces tumor responses in cervical cancer patients. Further studies are needed to confirm these results as well as to elucidate the mechanisms underlying these effects.[1]

References

A pilot study of perilymphatic leukocyte cytokine mixture (IRX-2) as neoadjuvant treatment for early stage cervical carcinoma. Dueñas-Gonzalez, A., Verastegui, E., Lopez-Graniel, C., Gonzalez, A., Mota, A., Barrera-Franco, J.L., Meneses, A., Chanona, J., de la Garza, J., Chavez-Blanco, A., Hadden, J.W. Int. Immunopharmacol. (2002) [Pubmed]

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