ObjectiveWe examined the role of gender, family, lifestyle and psychological factors in self-rated health.DesignCross-sectional study.SettingA total of 970 randomly selected students from 11 secondary schools in Lima and Callao, Peru, participated in 2014.Main outcome measureSelf-rated health was measured with a single item: ‘In general, how would you rate your health?’ Responses were arranged along a five-point Likert-type scale: ‘excellent’, ‘very good’, ‘good’, ‘fair’ and ‘poor’. The outcome variable was dichotomised as ‘good’ (excellent, very good or good) or ‘poor/fair’ (poor or fair).MethodsWe calculated adjusted ORs (AORs) and 95% CIs for poor/fair self-rated health using multivariate logistic regression analyses at 3-graded levels.Results32.5% of the respondents had fair/poor self-rated health, 23.7% of the total males and 40.0% of the total female samples. Males were less likely to have poor/fair self-rated health (AOR 0.61; CI 0.41 to 0.91). Poor family support strongly increased the likelihood of having poor/fair self-rated health (no support, (AOR 3.15; CI 1.63 to 6.09); low support, (AOR 2.50; CI 1.29 to 4.85)). The other associated variables were missed meals due to a shortage of food (AOR 1.97; CI 1.15 to 3.36), television watching during leisure time (AOR 1.70; CI 1.09 to 2.67), low physical activity (AOR 1.49; CI 1.03 to 2.15), school absenteeism (AOR 1.54; CI 1.03 to 2.31) and perceived life satisfaction (AOR 0.28; CI 0.15 to 0.25).ConclusionsGender, missing meals due to a shortage of food, family support, physical activity and life satisfaction influenced self-rated health among adolescents in Peru. Interventions that focus on promoting physical activity for at least 1 h each day for 3 or more days per week, food security and strengthening supportive family roles may improve self-rated health during adolescence.
The activation of CD137, also known as 4-1BB, has been identified as a promising strategy for next-generation immune therapeutics. However, cancer therapies based on activating antibodies to CD137 were discontinued by adverse events such as liver toxicity. To overcome those limitations, next generation antibody therapeutics using bispecific antibody approach has been developed by adjusting affinity, epitope, and valency. In this study, the anti-CD137 antibody with the binding epitope in the membrane-proximal region did not have CD137 cross-linking or T cell activating activity alone. However, when the anti-CD137 scFv was linked into a bispecific antibody with a tumor-associated antigen (TAA) targeting antibody, the anti-CD137 antibody strongly augmented T cell activation. We mined the anti-CD137 antibody, 1A10, which induces clustering-dependent agonism using screening of a phage library. 1A10 bound to the CD137 with a high affinity and induced signaling only in the presence of the Fc cross-linking anti-human IgG antibody. Various TAAx1A10 bispecific antibodies were generated by introducing 1A10 scFv into human IgGs targeting TAA. When the 1A10 was linked to TAA-specific antibodies in bispecific antibody format, 1A10 induced potent T cell activation and tumor-killing in a TAA dependent manner according to CD137 bioassays and PBMC based assays. To evaluate the competition on CD137 binding, we did epitope binning analysis with other anti-CD137 antibodies and CD137L. 1A10 binding inhibited further binding of utomilumab to CD137, but not the binding of urelumab or CD137L to CD137, suggesting that the 1A10 binding site is different from urelumab or CD137L. Further detailed epitope mapping study using a library of surface arginine or glutamic acid mutations on the CD137 via high-throughput FACS and NGS analysis revealed the binding sites of 1A10 mapped to CRD4. The site did not overlap with CD137L binding region, which explains why 1A10 did not compete with CD137L. The epitope site of 1A10 is also quite distinct from the urelumab binding site, which locates on the apical region of CD137. The 1A10 epitope site is partially overlapping with utomilumab binding sites on the CRD4 but does not bind to the CRD3, where utomilumab binds and competes with CD137L. In summary, 1A10, the anti-CD137 antibody with a unique epitope exhibited clustering dependent CD137 activation and potent anti-tumor activity via tumor-specific activation of CD137 in bispecific antibody format. Citation Format: Yangsoon Lee, Suyoun Lee, Yeunju Kim, Hyejin Chung, Kyungjin Park, Eunyoung Park, Kyeong-Su Park, Jinwon Jung, Byungje Sung, Jonghwa Won. A novel anti-CD137 antibody recognizing the membrane-proximal CD137 domain elicits potent anti-tumor T cell activity in a bispecific antibody format [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1850.
B7-H4 (B7x, VTCN1), a member of the B7-family, is overexpressed in majority of cancer patients with ovarian, endometrial and breast cancers. B7-H4 expression was also observed in tumor associated macrophages and implicated as an immune checkpoint regulating T cell responses. Although B7-H4 expression in normal tissues is quite limited, tumor-specific immune response by ABL103 would minimize potential adverse effects. ABL103, B7-H4 Grabody-T, is a First-in Class bispecific antibody targeting B7-H4 and 4-1BB and augments T cell function by a dual mechanism, i.e., 1) blocks the B7-H4 mediated T cell inhibition, and 2) elicits superior T cell activation through B7-H4-dependent 4-1BB clustering. Our data showed that simultaneous binding of B7-H4 and 4-1BB by ABL103 led to potent in vitro T cell activation only in the presence of B7-H4 expressing tumor cells. In the established tumor model, ABL103 potently inhibited tumor progression in a dose-dependent manner and showed higher rate of complete remission (CR) at 2 and 10 mg/kg dose groups. Moreover, mice were protected from the tumor re-challenge 3 months after cessation of ABL103 treatment, suggesting long-term memory has been established. In 4-week pilot tox study using cynomolgus monkeys, ABL103 was tolerable up to 100 mg/kg dosed weekly with no ABL103-related toxicity observations. To understand the relationship of target expression, expression of B7-H4, CD4, CD8, PD-L1, and 4-1BB was examined in 142 ovarian cancer patient biopsies. About 83% of ovarian cancer patient tissues showed B7-H4 positive staining and 62% of them showed strong positive. In addition, the staining of 4-1BB as well as CD4 and CD8 T cells were observed in both tumor nest and stroma, suggesting that cross-linking of B7-H4 and 4-1BB is feasible in tumor microenvironment. Overall, ABL103 has a strong in vitro and vivo anti-tumor activity and good safety profile via B7-H4-dependent 4-1BB activation. This strongly suggests ABL103 is a promising therapeutic agent potentially benefitting patients with B7-H4 overexpression. Citation Format: Kyungjin Park, Yangsoon Lee, Saeyi Lim, Kyeongsu Park, Eunjung Kim, Hanbyul Lee, Jiseon Yoo, Youngdon Pak, Yeunju Kim, Minji Ko, Jonghwa Won. ABL103, A novel T-cell engaging bispecific antibody, exhibits potent in vitro and vivo antitumor activity and low toxicity via B7-H4 dependent 4-1BB activation in tumor microenvironment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 4246.
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