| Title |
Clinical and immunologic evaluation of three metastatic melanoma patients treated with autologous melanoma-reactive TCR-transduced T cells
|
|---|---|
| Published in |
Cancer Immunology, Immunotherapy, October 2017
|
| DOI | 10.1007/s00262-017-2073-0 |
| Pubmed ID | |
| Authors |
Tamson Moore, Courtney Regan Wagner, Gina M. Scurti, Kelli A. Hutchens, Constantine Godellas, Ann Lau Clark, Elizabeth Motunrayo Kolawole, Lance M. Hellman, Nishant K. Singh, Fernando A. Huyke, Siao-Yi Wang, Kelly M. Calabrese, Heather D. Embree, Rimas Orentas, Keisuke Shirai, Emilia Dellacecca, Elizabeth Garrett-Mayer, Mingli Li, Jonathan M. Eby, Patrick J. Stiff, Brian D. Evavold, Brian M. Baker, I. Caroline Le Poole, Boro Dropulic, Joseph I. Clark, Michael I. Nishimura |
| Abstract |
Malignant melanoma incidence has been increasing for over 30 years, and despite promising new therapies, metastatic disease remains difficult to treat. We describe preliminary results from a Phase I clinical trial (NCT01586403) of adoptive cell therapy in which three patients received autologous CD4(+) and CD8(+) T cells transduced with a lentivirus carrying a tyrosinase-specific TCR and a marker protein, truncated CD34 (CD34t). This unusual MHC Class I-restricted TCR produces functional responses in both CD4(+) and CD8(+) T cells. Parameters monitored on transduced T cells included activation (CD25, CD69), inhibitory (PD-1, TIM-3, CTLA-4), costimulatory (OX40), and memory (CCR7) markers. For the clinical trial, T cells were activated, transduced, selected for CD34t(+) cells, then re-activated, and expanded in IL-2 and IL-15. After lymphodepleting chemotherapy, patients were given transduced T cells and IL-2, and were followed for clinical and biological responses. Transduced T cells were detected in the circulation of three treated patients for the duration of observation (42, 523, and 255 days). Patient 1 tolerated the infusion well but died from progressive disease after 6 weeks. Patient 2 had a partial response by RECIST criteria then progressed. After progressing, Patient 2 was given high-dose IL-2 and subsequently achieved complete remission, coinciding with the development of vitiligo. Patient 3 had a mixed response that did not meet RECIST criteria for a clinical response and developed vitiligo. In two of these three patients, adoptive transfer of tyrosinase-reactive TCR-transduced T cells into metastatic melanoma patients had clinical and/or biological activity without serious adverse events. |
X Demographics
The data shown below were collected from the profiles of 4 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Australia | 1 | 25% |
| United States | 1 | 25% |
| Unknown | 2 | 50% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 3 | 75% |
| Science communicators (journalists, bloggers, editors) | 1 | 25% |
Mendeley readers
The data shown below were compiled from readership statistics for 59 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 59 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 10 | 17% |
| Researcher | 10 | 17% |
| Student > Bachelor | 5 | 8% |
| Student > Doctoral Student | 4 | 7% |
| Student > Postgraduate | 3 | 5% |
| Other | 9 | 15% |
| Unknown | 18 | 31% |
| Readers by discipline | Count | As % |
|---|---|---|
| Immunology and Microbiology | 13 | 22% |
| Medicine and Dentistry | 10 | 17% |
| Biochemistry, Genetics and Molecular Biology | 6 | 10% |
| Agricultural and Biological Sciences | 3 | 5% |
| Chemistry | 3 | 5% |
| Other | 6 | 10% |
| Unknown | 18 | 31% |
Attention Score in Context
This research output has an Altmetric Attention Score of 3. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 06 November 2017.
All research outputs
#12,996,766
of 23,006,268 outputs
Outputs from Cancer Immunology, Immunotherapy
#1,833
of 2,895 outputs
Outputs of similar age
#154,147
of 328,577 outputs
Outputs of similar age from Cancer Immunology, Immunotherapy
#14
of 34 outputs
Altmetric has tracked 23,006,268 research outputs across all sources so far. This one is in the 43rd percentile – i.e., 43% of other outputs scored the same or lower than it.
So far Altmetric has tracked 2,895 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.2. This one is in the 36th percentile – i.e., 36% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 328,577 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 52% of its contemporaries.
We're also able to compare this research output to 34 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 58% of its contemporaries.