A Novel Combined Conjugate Therapeutic Cancer Vaccine, Recombinant EGF-CRM197, in Patients With Advanced Solid Tumors: A Phase I Clinical Study
IntroductionThe therapeutic cancer vaccine recombinant Epidermal Growth Factor (EGF)-CRM197 is a novel combined conjugate EGF with CRM197 as a carrier protein. Immunization with the EGF-CRM197 vaccine can induce high levels of neutralizing anti-EGF antibodies that inhibit EGF/EGFR signaling and ther...
Guardado en:
| Autores principales: | , , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Frontiers Media S.A.
2021
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/be846440cbd8444a941e546a2d628629 |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:be846440cbd8444a941e546a2d628629 |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:be846440cbd8444a941e546a2d6286292021-11-05T14:42:54ZA Novel Combined Conjugate Therapeutic Cancer Vaccine, Recombinant EGF-CRM197, in Patients With Advanced Solid Tumors: A Phase I Clinical Study2234-943X10.3389/fonc.2021.745699https://doaj.org/article/be846440cbd8444a941e546a2d6286292021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fonc.2021.745699/fullhttps://doaj.org/toc/2234-943XIntroductionThe therapeutic cancer vaccine recombinant Epidermal Growth Factor (EGF)-CRM197 is a novel combined conjugate EGF with CRM197 as a carrier protein. Immunization with the EGF-CRM197 vaccine can induce high levels of neutralizing anti-EGF antibodies that inhibit EGF/EGFR signaling and thereby suppress growth of tumors that rely on this signaling pathway. Herein, we characterize the humoral immune responses elicited by the recombinant EGF-CRM197 vaccine in patients with advanced solid tumors in a phase I clinical trial and assess the safety, tolerability, and immunogenicity of this vaccine (CTR20190473).MethodsA total of 16 subjects were enrolled in this study. Under 6 + 3 design, patients in each dosing cohort were administrated subcutaneously at a dosage of 0.4 mg, 0.8 mg, and 1.6 mg, respectively. The patients received vaccinations for immune induction (once a week for 4 consecutive weeks) and booster vaccinations (once every 4 weeks). Safety evaluation was performed 1 week after the immune induction. Booster vaccination was given until the occurrence of disease progression, intolerance, withdrawal of informed consent by the patient, or negative result of anti-EGF test after two booster vaccinations.ResultsVaccination with EGF-CRM197 is safe and well-tolerated in patients with advanced solid tumors. Adverse reactions at the injection site were the most common adverse events (AEs) in recipients. No severe adverse reactions post vaccination were observed in the present study. Vaccinated patients developed a robust neutralizing antibody response triggered by EGF-CRM197 that significantly reduced the levels of EGF in serum. For lung cancer patients who were super good antibody responders (sGAR) to EGF-CRM197, the median progress-free survival (PFS) was 4.83 months, significantly longer than that of the good antibody responder (GAR) patients with lung cancer whose median PFS was 2.10 months (P=0.0018). The median overall survival (OS) of GAR lung cancer patients was 10.67 months while the OS) for sGAR lung cancer patients was not reached until analysis was performed. The median follow-up of the sGAR lung cancer patients was 14.6 months.ConclusionOur study demonstrates that the recombinant EGF-CRM197 therapeutic cancer vaccine can induce a good immune response in patients with advanced solid tumors and is safe and well tolerated, which ensures further clinical development of the vaccine for extending the survival time of EGF-CRM197 sensitive patients with advanced solid tumors.Clinical Trial Registrationhttp://www.chinadrugtrials.org.cn, identifier CTR20190473, EGF-CRM197.An-Wen XiongJue-Min FangSheng-Xiang RenWei LiJing WangYu ZhaoGuo-You ChenQing XuCai-Cun ZhouFrontiers Media S.A.articletherapeutic cancer vaccineEGF-CRM197Solid tumorsclinical trialimmunotherapyNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENFrontiers in Oncology, Vol 11 (2021) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
therapeutic cancer vaccine EGF-CRM197 Solid tumors clinical trial immunotherapy Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 |
| spellingShingle |
therapeutic cancer vaccine EGF-CRM197 Solid tumors clinical trial immunotherapy Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 An-Wen Xiong Jue-Min Fang Sheng-Xiang Ren Wei Li Jing Wang Yu Zhao Guo-You Chen Qing Xu Cai-Cun Zhou A Novel Combined Conjugate Therapeutic Cancer Vaccine, Recombinant EGF-CRM197, in Patients With Advanced Solid Tumors: A Phase I Clinical Study |
| description |
IntroductionThe therapeutic cancer vaccine recombinant Epidermal Growth Factor (EGF)-CRM197 is a novel combined conjugate EGF with CRM197 as a carrier protein. Immunization with the EGF-CRM197 vaccine can induce high levels of neutralizing anti-EGF antibodies that inhibit EGF/EGFR signaling and thereby suppress growth of tumors that rely on this signaling pathway. Herein, we characterize the humoral immune responses elicited by the recombinant EGF-CRM197 vaccine in patients with advanced solid tumors in a phase I clinical trial and assess the safety, tolerability, and immunogenicity of this vaccine (CTR20190473).MethodsA total of 16 subjects were enrolled in this study. Under 6 + 3 design, patients in each dosing cohort were administrated subcutaneously at a dosage of 0.4 mg, 0.8 mg, and 1.6 mg, respectively. The patients received vaccinations for immune induction (once a week for 4 consecutive weeks) and booster vaccinations (once every 4 weeks). Safety evaluation was performed 1 week after the immune induction. Booster vaccination was given until the occurrence of disease progression, intolerance, withdrawal of informed consent by the patient, or negative result of anti-EGF test after two booster vaccinations.ResultsVaccination with EGF-CRM197 is safe and well-tolerated in patients with advanced solid tumors. Adverse reactions at the injection site were the most common adverse events (AEs) in recipients. No severe adverse reactions post vaccination were observed in the present study. Vaccinated patients developed a robust neutralizing antibody response triggered by EGF-CRM197 that significantly reduced the levels of EGF in serum. For lung cancer patients who were super good antibody responders (sGAR) to EGF-CRM197, the median progress-free survival (PFS) was 4.83 months, significantly longer than that of the good antibody responder (GAR) patients with lung cancer whose median PFS was 2.10 months (P=0.0018). The median overall survival (OS) of GAR lung cancer patients was 10.67 months while the OS) for sGAR lung cancer patients was not reached until analysis was performed. The median follow-up of the sGAR lung cancer patients was 14.6 months.ConclusionOur study demonstrates that the recombinant EGF-CRM197 therapeutic cancer vaccine can induce a good immune response in patients with advanced solid tumors and is safe and well tolerated, which ensures further clinical development of the vaccine for extending the survival time of EGF-CRM197 sensitive patients with advanced solid tumors.Clinical Trial Registrationhttp://www.chinadrugtrials.org.cn, identifier CTR20190473, EGF-CRM197. |
| format |
article |
| author |
An-Wen Xiong Jue-Min Fang Sheng-Xiang Ren Wei Li Jing Wang Yu Zhao Guo-You Chen Qing Xu Cai-Cun Zhou |
| author_facet |
An-Wen Xiong Jue-Min Fang Sheng-Xiang Ren Wei Li Jing Wang Yu Zhao Guo-You Chen Qing Xu Cai-Cun Zhou |
| author_sort |
An-Wen Xiong |
| title |
A Novel Combined Conjugate Therapeutic Cancer Vaccine, Recombinant EGF-CRM197, in Patients With Advanced Solid Tumors: A Phase I Clinical Study |
| title_short |
A Novel Combined Conjugate Therapeutic Cancer Vaccine, Recombinant EGF-CRM197, in Patients With Advanced Solid Tumors: A Phase I Clinical Study |
| title_full |
A Novel Combined Conjugate Therapeutic Cancer Vaccine, Recombinant EGF-CRM197, in Patients With Advanced Solid Tumors: A Phase I Clinical Study |
| title_fullStr |
A Novel Combined Conjugate Therapeutic Cancer Vaccine, Recombinant EGF-CRM197, in Patients With Advanced Solid Tumors: A Phase I Clinical Study |
| title_full_unstemmed |
A Novel Combined Conjugate Therapeutic Cancer Vaccine, Recombinant EGF-CRM197, in Patients With Advanced Solid Tumors: A Phase I Clinical Study |
| title_sort |
novel combined conjugate therapeutic cancer vaccine, recombinant egf-crm197, in patients with advanced solid tumors: a phase i clinical study |
| publisher |
Frontiers Media S.A. |
| publishDate |
2021 |
| url |
https://doaj.org/article/be846440cbd8444a941e546a2d628629 |
| work_keys_str_mv |
AT anwenxiong anovelcombinedconjugatetherapeuticcancervaccinerecombinantegfcrm197inpatientswithadvancedsolidtumorsaphaseiclinicalstudy AT jueminfang anovelcombinedconjugatetherapeuticcancervaccinerecombinantegfcrm197inpatientswithadvancedsolidtumorsaphaseiclinicalstudy AT shengxiangren anovelcombinedconjugatetherapeuticcancervaccinerecombinantegfcrm197inpatientswithadvancedsolidtumorsaphaseiclinicalstudy AT weili anovelcombinedconjugatetherapeuticcancervaccinerecombinantegfcrm197inpatientswithadvancedsolidtumorsaphaseiclinicalstudy AT jingwang anovelcombinedconjugatetherapeuticcancervaccinerecombinantegfcrm197inpatientswithadvancedsolidtumorsaphaseiclinicalstudy AT yuzhao anovelcombinedconjugatetherapeuticcancervaccinerecombinantegfcrm197inpatientswithadvancedsolidtumorsaphaseiclinicalstudy AT guoyouchen anovelcombinedconjugatetherapeuticcancervaccinerecombinantegfcrm197inpatientswithadvancedsolidtumorsaphaseiclinicalstudy AT qingxu anovelcombinedconjugatetherapeuticcancervaccinerecombinantegfcrm197inpatientswithadvancedsolidtumorsaphaseiclinicalstudy AT caicunzhou anovelcombinedconjugatetherapeuticcancervaccinerecombinantegfcrm197inpatientswithadvancedsolidtumorsaphaseiclinicalstudy AT anwenxiong novelcombinedconjugatetherapeuticcancervaccinerecombinantegfcrm197inpatientswithadvancedsolidtumorsaphaseiclinicalstudy AT jueminfang novelcombinedconjugatetherapeuticcancervaccinerecombinantegfcrm197inpatientswithadvancedsolidtumorsaphaseiclinicalstudy AT shengxiangren novelcombinedconjugatetherapeuticcancervaccinerecombinantegfcrm197inpatientswithadvancedsolidtumorsaphaseiclinicalstudy AT weili novelcombinedconjugatetherapeuticcancervaccinerecombinantegfcrm197inpatientswithadvancedsolidtumorsaphaseiclinicalstudy AT jingwang novelcombinedconjugatetherapeuticcancervaccinerecombinantegfcrm197inpatientswithadvancedsolidtumorsaphaseiclinicalstudy AT yuzhao novelcombinedconjugatetherapeuticcancervaccinerecombinantegfcrm197inpatientswithadvancedsolidtumorsaphaseiclinicalstudy AT guoyouchen novelcombinedconjugatetherapeuticcancervaccinerecombinantegfcrm197inpatientswithadvancedsolidtumorsaphaseiclinicalstudy AT qingxu novelcombinedconjugatetherapeuticcancervaccinerecombinantegfcrm197inpatientswithadvancedsolidtumorsaphaseiclinicalstudy AT caicunzhou novelcombinedconjugatetherapeuticcancervaccinerecombinantegfcrm197inpatientswithadvancedsolidtumorsaphaseiclinicalstudy |
| _version_ |
1718444253019897856 |