دورية أكاديمية
Implementing preclinical study findings to protocol design: translational studies with alloreactive CTL for gliomas.
| العنوان: | Implementing preclinical study findings to protocol design: translational studies with alloreactive CTL for gliomas. |
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| المؤلفون: | Hickey MJ, Malone CC, Erickson KE, Gomez GG, Young EL, Liau LM, Prins RM, Kruse CA |
| المصدر: | American journal of translational research [Am J Transl Res] 2012; Vol. 4 (1), pp. 114-26. Date of Electronic Publication: 2012 Jan 10. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: e-Century Pub. Corp Country of Publication: United States NLM ID: 101493030 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1943-8141 (Electronic) Linking ISSN: 19438141 NLM ISO Abbreviation: Am J Transl Res Subsets: PubMed not MEDLINE |
| أسماء مطبوعة: | Original Publication: Madison, WI : e-Century Pub. Corp. |
| مستخلص: | We are accruing patients to a Phase I dose escalation cellular therapy trial (www.clinicaltrials.gov, NCT01144247) involving intratumoral placement of alloreactive cytotoxic T lymphocytes (alloCTL) for recurrent gliomas. The trial is being conducted to confirm the findings of a prior pilot study that indicated this adjuvant therapy may be beneficial in extending survival of recurrent WHO grade III gliomas. To reduce costs of the cellular therapy, we tested a number of synthetic tissue culture media and found the AIM-V growth medium superior for their growth. We also moved the production of the alloCTL from artificial capillary systems to less expensive tissue culture bags. To standardize alloCTL infusates used for therapy, release criteria of ≥60% CD3+ and ≥60% viability were established that consistently translated to a 4 hr cytotoxicity of ≥30% at a 30:1 effector to target ratio. To allow time for completion of quality control testing and transport to the infusion site, we determined that 30,000 IU of human recombinant Interleukin-2 in the cellular infusates sufficiently retained cell viability and cytotoxicity to allow a 10 hr expiration time to be placed on the infusates. We identified a cytotoxic T cell subset, CD3+/CD8+/CD69+, that demonstrated upregulated IFN-γ production upon exposure to relevant target cells. The phenotypic identification of this T cell subset was indicative of robust in vitro cytotoxic function and thus will be followed to determine if it correlates with patient immune response to treatment. Finally, other therapeutic agents routinely used for glioma treatment were integrated into an analysis of alloCTL cytotoxic functionality. Temozolomide and bevacizumab do not adversely affect cytotoxic function of the alloCTL in the short-term, thus providing rationale for further investigating combinatorial chemo-immunotherapy for gliomas. |
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| معلومات مُعتمدة: | R01 CA121258 United States CA NCI NIH HHS; R01 CA125244 United States CA NCI NIH HHS; R01 CA154256 United States CA NCI NIH HHS |
| فهرسة مساهمة: | Keywords: Astrocytoma; CTL; adoptive immunotherapy; bevacizumab; cellular therapy; glioma; immunotherapy; temozolomide |
| سلسلة جزيئية: | ClinicalTrials.gov NCT01144247 |
| تواريخ الأحداث: | Date Created: 20120221 Date Completed: 20121002 Latest Revision: 20211021 |
| رمز التحديث: | 20221213 |
| مُعرف محوري في PubMed: | PMC3276381 |
| PMID: | 22347526 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1943-8141 |
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