| Title |
Therapeutic HPV Cancer Vaccine Targeted to CD40 Elicits Effective CD8+ T-cell Immunity
|
|---|---|
| Published in |
Cancer Immunology Research, October 2016
|
| DOI | 10.1158/2326-6066.cir-16-0128 |
| Pubmed ID | |
| Authors |
Wenjie Yin, Dorothée Duluc, HyeMee Joo, Yaming Xue, Chao Gu, Zhiqing Wang, Lei Wang, Richard Ouedraogo, Lance Oxford, Amelia Clark, Falguni Parikh, Seunghee Kim-Schulze, LuAnn Thompson-Snipes, Sang-Yull Lee, Clay Beauregard, Jung-Hee Woo, Sandra Zurawski, Andrew G. Sikora, Gerard Zurawski, SangKon Oh |
| Abstract |
Human papillomavirus (HPV), particularly HPV16 and HPV18, can cause cancers in diverse anatomical sites, including the anogenital and oropharyngeal (throat) regions. Therefore, development of safe and clinically effective therapeutic vaccines is an important goal. Herein, we show that a recombinant fusion protein of a humanized antibody to CD40 fused to HPV16.E6/7 (αCD40-HPV16.E6/7) can evoke HPV16.E6/7-specific CD8+ and CD4+ T-cell responses in head-and-neck cancer patients in vitro and in human CD40 transgenic (hCD40tg) mice in vivo. The combination of αCD40-HPV16.E6/7 and poly(I:C) efficiently primed HPV16.E6/7-specific T-cells, particularly CD8+ T-cells, in hCD40tg mice. Inclusion of montanide enhanced HPV16.E6/7-specific CD4+, but not CD8+, T-cell responses. Poly(I:C) plus αCD40-HPV16.E6/7 was sufficient to mount both preventative and therapeutic immunity against TC-1 tumors in hCD40tg mice, significantly increasing the frequency of HPV16-specific CD8+ CTLs in the tumors, but not in peripheral blood. In line with this, tumor volume inversely correlated with the frequency of HPV16.E6/7-specific CD8+ T-cells in tumors, but not in blood. These data suggest that CD40-targeting vaccines for HPV-associated malignancies can provide a highly immunogenic platform with a strong likelihood of clinical benefit. Data from this study offer strong support for the development of CD40-targeting vaccines for other cancers in the future. |
X Demographics
The data shown below were collected from the profiles of 2 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 1 | 50% |
| Unknown | 1 | 50% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 2 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 49 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 49 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 12 | 24% |
| Student > Ph. D. Student | 8 | 16% |
| Student > Doctoral Student | 4 | 8% |
| Professor | 3 | 6% |
| Other | 3 | 6% |
| Other | 7 | 14% |
| Unknown | 12 | 24% |
| Readers by discipline | Count | As % |
|---|---|---|
| Immunology and Microbiology | 15 | 31% |
| Medicine and Dentistry | 8 | 16% |
| Biochemistry, Genetics and Molecular Biology | 7 | 14% |
| Agricultural and Biological Sciences | 2 | 4% |
| Chemistry | 2 | 4% |
| Other | 1 | 2% |
| Unknown | 14 | 29% |
Attention Score in Context
This research output has an Altmetric Attention Score of 7. 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 12 December 2023.
All research outputs
#4,858,568
of 25,463,724 outputs
Outputs from Cancer Immunology Research
#557
of 1,571 outputs
Outputs of similar age
#74,797
of 332,145 outputs
Outputs of similar age from Cancer Immunology Research
#13
of 61 outputs
Altmetric has tracked 25,463,724 research outputs across all sources so far. Compared to these this one has done well and is in the 79th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
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We're also able to compare this research output to 61 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 77% of its contemporaries.