Abstract |
Naptumomab estafenatox/ABR-217620/ ANYARA (Nap) has been evaluated in clinical phase 1 and 2/3 studies. RCC patients in the phase 2/3 trial were randomized 1:1 in an open label study to receive Nap+IFN-α or IFN-α. In this study, we analyzed the UK patients for their immunological response in relation to prolonged overall survival (OS). We found that Nap-specific T cells were reduced after 3 treatment days in patients' peripheral blood. Levels of both Nap-specific CD4+ and CD8+ T cells were significantly higher 8 days after the first treatment. Patients with such pattern of reduction and expansion of Nap-binding T cells also showed increased levels of IL-2 and IFN-γ in plasma 3 hours after the first Nap treatment. In addition, Nap caused an increase of IL-6, IL-10 and TNF-α. The patients in the UK subset showed a tendency of OS benefit after Nap treatment. Most Nap treated patients with long OS had low baseline IL-6 and normal levels of anti-SEA/E-120 antibodies. Furthermore, patients with pronounced Nap induced IL-2 and T cell expansion had long OS. In conclusion, patients with low baseline IL-6 and normal anti-SEA/E-120 may respond well to Nap by T cell activation and expansion paving the way for anti-tumour effects.
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Authors | Eyad Elkord, Deborah J Burt, Anette Sundstedt, Örjan Nordle, Gunnar Hedlund, Robert E Hawkins |
Journal | Oncotarget
(Oncotarget)
Vol. 6
Issue 6
Pg. 4428-39
(Feb 28 2015)
ISSN: 1949-2553 [Electronic] United States |
PMID | 25669986
(Publication Type: Clinical Trial, Phase II, Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial)
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Chemical References |
- Antibodies, Monoclonal
- Antineoplastic Agents
- Enterotoxins
- IL6 protein, human
- Immunoconjugates
- Interferon-alpha
- Interleukin-6
- naptumomab estafenatox
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Topics |
- Adolescent
- Adult
- Aged
- Aged, 80 and over
- Antibodies, Monoclonal
(therapeutic use)
- Antineoplastic Agents
(therapeutic use)
- Carcinoma, Renal Cell
(drug therapy, immunology, mortality)
- Enterotoxins
(therapeutic use)
- Female
- Flow Cytometry
- Humans
- Immunoconjugates
(therapeutic use)
- Interferon-alpha
(therapeutic use)
- Interleukin-6
(blood)
- Kaplan-Meier Estimate
- Kidney Neoplasms
(drug therapy, immunology, mortality)
- Male
- Middle Aged
- T-Lymphocyte Subsets
(drug effects)
- T-Lymphocytes
(drug effects)
- Young Adult
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