Novel OK-432-conjugated Tumor Vaccines Induce Tumor-specific Immunity against Murine Tongue Cancer

2003 ◽  
Vol 82 (8) ◽  
pp. 636-640
Author(s):  
X. Li ◽  
H. Bukawa ◽  
M. Hirota ◽  
Y. Tsuyuki ◽  
S. Omura ◽  
...  

Priming with tumor antigens is one of the most important strategies in cancer immunotherapy. To enhance tumor antigenicity, OK-432, a streptococcal preparation, was coupled to squamous cell carcinoma (KLN-205) by means of a 0.2% glutaraldehyde method. The purpose of this study was to investigate whether OK-432-conjugated tumor vaccines could induce tumor-specific immunity. Our originally developed mouse tongue cancer model was used throughout this work for the analysis of antitumor effects. Prepared OK-432-conjugated KLN-205 vaccines were immunized 3 times to DBA/2 mice. The results showed that the KLN-205 vaccines induced cytolytic activity and strongly suppressed both KLN-205 tumor incidence and growth, and survival of the mice was improved. Moreover, the histological results showed that a greater number of lymphocytes had infiltrated around tumor cells by 24 hours after tumor inoculation in the vaccine group. These results suggest that immunizations with KLN-205 vaccines increase the antitumor effects against tongue cancer.

1999 ◽  
Vol 57 (8) ◽  
pp. 965-972 ◽  
Author(s):  
Susumu Omura ◽  
Yoshiharu Tsuyuki ◽  
Shinsuke Ohta ◽  
Hiroki Bukawa ◽  
Kiyohide Fujita

Nanophotonics ◽  
2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Zhe Sun ◽  
Taojian Fan ◽  
Quan Liu ◽  
Luodan Huang ◽  
Weibin Hu ◽  
...  

Abstract Personalized therapeutic vaccines against immune desert tumors are an increasingly important field in current cancer immunotherapy. However, limitations in neoantigen recognition, impotent immune cells, and a lack of intratumoral infiltrated lymphocytes pose challenges for the cancer vaccines. Resected tumors contain various of patient-specific tumor autoantigens (TA), and its derived photonanovaccines have unique competency to overcome abovementioned barriers. We constructed a novel personalized photonanovaccine (B@TA-R848) with surgically sourced TA modified on two-dimensional boron nanosheets (BNSs) via polydopamine coating and loaded with immune adjuvant R848. B@TA-R848 has good properties of drug delivery and release, photoacoustic imaging, photothermal effect, and biocompatibility. In a mouse triple-negative breast cancer model, B@TA-R848-based photonanovaccine induced effective systemic antitumor immune responses, altered the local tumor microenvironment, and increased the intratumoral infiltration of immune cells. The combined photo immunotherapy could significantly inhibit tumor growth, recurrence, and metastasis. This work develops a novel photonanovaccine for low immunogenicity and high metastatic potential tumors, which is of great significance for exploring the clinical development of personalized tumor vaccines against immune desert tumors.


1997 ◽  
Vol 89 (2) ◽  
pp. 286-290 ◽  
Author(s):  
H ITAMOCHI ◽  
J KIGAWA ◽  
Y MINAGAWA ◽  
X CHENG ◽  
M OKADA ◽  
...  

2018 ◽  
Vol 5 (4) ◽  
pp. 87 ◽  
Author(s):  
Chris Weir ◽  
Annika Oksa ◽  
Jennifer Millar ◽  
Miles Alexander ◽  
Nicola Kynoch ◽  
...  

Canine cancer rates are similar to humans, though the therapeutic options might be limited. Inducing a patient’s own immune system to have an anti-tumor response is an attractive approach to cancer therapy. In this safety study, autologous tumor vaccines produced specifically for each canine patient were combined with Advax™, a novel non-inflammatory immunomodulator and vaccine adjuvant and were tested for safety in a diverse range of patient presentations alone or in combination with other treatments. Canine patients had their tumor biopsied, debulked or resected and the tumor antigens were processed into an autologous vaccine formulated with Advax™ adjuvant with or without rhizavidin as an additional immune stimulant. Patients treated early in the trial received two intramuscular (IM) doses, 2 weeks apart. As the study progressed and no issues of safety were observed, the protocol was changed to weekly vaccinations for 4 weeks followed by monthly booster shots. Over the 150 I.M injections delivered to date, the vaccine was found to be very safe and no significant adverse reactions were observed. These results justify ongoing development and future controlled studies of this autologous vaccine approach.


Gene Therapy ◽  
2015 ◽  
Vol 23 (1) ◽  
pp. 38-49 ◽  
Author(s):  
M-C Chang ◽  
Y-L Chen ◽  
Y-C Chiang ◽  
T-C Chen ◽  
Y-C Tang ◽  
...  

2020 ◽  
Vol 118 ◽  
pp. 104846
Author(s):  
Qingwei Zheng ◽  
Jing Sun ◽  
Wenli Li ◽  
Shuangnan Li ◽  
Kai Zhang

1999 ◽  
Vol 90 (9) ◽  
pp. 1000-1006 ◽  
Author(s):  
Hiroshi Terasawa ◽  
Hiroshi Tanimura ◽  
Mikihito Nakamori ◽  
Takuya Tsunoda ◽  
Makoto Iwahashi ◽  
...  

2013 ◽  
Vol 136 (0) ◽  
pp. 62-69
Author(s):  
Ying-Ying Wu ◽  
Toru Hirano ◽  
Junko Yamamoto ◽  
Guang-Wu Huang ◽  
Seiji Yamamoto ◽  
...  

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 3031-3031
Author(s):  
S. Parker ◽  
D. Berman ◽  
K. L. Bennett ◽  
S. Alaparthy ◽  
Z. Tsuchihashi ◽  
...  

3031 Background: Ipilimumab is an anti-CTLA-4 monoclonal antibody (Ab) that overcomes T-cell suppression. In this phase II study (CA184004), humoral and cellular responses were assessed in ipilimumab-treated pts with unresectable stage III/IV melanoma. Methods: Ipilimumab 3 or 10 mg/kg was given every 3 weeks x 4. Tetanus boosters were given ≤10 days pre-treatment. Influenza and pneumococcal vaccines were given 5 days after first ipilimumab dose. Tetanus, anti-influenza, and anti-pneumococcal Ab levels were assessed at pre-dose and Wk 7. Humoral response to 5 tumor antigens (Ag) and a control Ag (DHFR) were examined at baseline (BL) and at Wks 4, 8–9, and 12. DTH skin tests were given at pre-dose and Wk 4, with responses recorded 15 minutes (min) and 24–72 hours (hrs) post-test. Peripheral T-cell populations were evaluated through flow cytometry at BL, Wk 4, and Wk 12. Results: Pts received ipilimumab 3 (n = 40) or 10 mg/kg (n = 42). Increases from BL in humoral responses to pneumococcal (40–50/78 pts, depending on Ab) and tetanus (58/78 pts) vaccines were noted, even in pts who did not receive on-study pneumococcal (4–9 pts) or tetanus (7 pts) vaccines. Increased humoral response to influenza only occurred in pts receiving the influenza vaccine. Maximum increase from BL of ≥ 5-fold titer (clinically meaningful threshold) in humoral response to tumor Ag MELANA (23.2% of pts), SSX2 (20.3%), NYES01 (18.8%), MAGEA4 (10.1%), and P53 (4.3%) (DHFR, 4.3%) was noted without tumor vaccines. Tumor Ag response was not associated with clinical activity (complete or partial response, or stable disease ≥ 24 wks). Increased DTH reactions were noted for tetanus, 24–72 hrs (3 mg/kg: 5/7 pts; 10 mg/kg: 3/6 pts); tuberculin, 15 min (3 mg/kg: 7/15 pts; 10 mg/kg: 4/15 pts); Candida, 15 min (3 mg/kg: 4/6 pts; 10 mg/kg: 2/7 pts); and Trichophyton, 15 min (3 mg/kg: 3/4 pts; 10 mg/kg: 2/5 pts). Significant increases from BL in percents of HLA-DR+ CD4+ (p = 9.3x10-7), HLA-DR+ CD8+ (p = 0.018), and ICOS+ CD4+ (p = 0.0027) effector T cells were noted. Conclusions: Humoral immunity in ipilimumab-treated pts increased (± vaccination) in an Ag-dependent manner and cellular immunity was enhanced. Change in tumor Ag response was not associated with clinical activity. [Table: see text]


2017 ◽  
Vol 35 (7_suppl) ◽  
pp. 151-151
Author(s):  
Christopher C. DeRenzo ◽  
Phuong Nguyen ◽  
Stephen Gottschalk

151 Background: T-cell therapy for cancer faces several challenges, including limited T-cell expansion at tumor sites, and lack of unique tumor antigens that are not expressed in normal tissues. To overcome the first obstacle, we developed Engager (ENG) T cells, which secrete bispecific molecules consisting of single chain variable fragments specific for CD3 and a tumor antigen. ENG T cells have the unique ability to redirect bystander T cells to tumors, amplifying antitumor effects. Costimulatory chimeric antigen receptors (CoCARs) are one potential strategy to restrict full T-cell activation to tumor sites that express a unique "antigen address." The goal of this project was now to generate T cells that express engager molecules and CoCARs (ENG/CoCAR T cells), which recognize distinct tumor antigens, and evaluate their effector function. Methods: We focused on two tumor antigens, EphA2 and HER2, which are expressed in a broad range of solid tumors. RD114-pseudotyped retroviral particles encoding an EphA2-ENG or a HER2-CoCAR were used to transduce CD3/CD28-activated human T cells. Transduced T cells were cocultured with EphA2+/HER2- or EphA2+/HER2+ tumor cells. Results: Both EphA2-ENG and EphA2-ENG/HER2-CoCAR T cells were activated by EphA2+ targets, as judged by IFNγ secretion. EphA2-ENG T cells secreted little IL-2 and died after one stimulation with EphA2+/HER2- or EphA2+/HER2+ tumor cells. In contrast, EphA2-ENG/HER2-CoCAR T cells secreted high levels of IL-2 and proliferated when stimulated with EphA2+/HER2+ cells. Little IL-2 secretion and no proliferation was observed after stimulation of the same T cells with EphA2+/HER2- cells, indicating these T cells are only fully activated in the presence of both target antigens. Upon repeated stimulation with EphA2+/HER2+ tumor cells, EphA2-ENG/HER2-CoCAR T cells continued to secrete IL-2 and proliferate without the addition of external cytokines for at least 10 weeks. Conclusions: EphA2-ENG/HER2-CoCAR T cells demonstrated robust dual antigen dependent IL-2 secretion, and continued proliferation upon repeat stimulation with EphA2+/HER2+ cells. Thus, providing antigen-specific costimulation is a potential strategy to improve the safety and efficacy of T-cell therapy for cancer.


Sign in / Sign up

Export Citation Format

Share Document