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Conventional cancer therapies such as chemotherapy are non-selective and induce immune system anergy, which lead to serious side effects and tumor relapse. It is a challenge to prime the body's immune system in the cancer-bearing subject to produce cancer antigen-targeting antibodies, as most tumor-associated antigens are expressed abundantly in cancer cells and some of normal cells. This study illustrates how hapten-based pre-immunization (for anti-hapten antibodies production) combined with cancer receptor labeling with hapten antigen constructs can elicit antibody-dependent cellular phagocytosis (ADCP). Thus, the hapten antigen 2,4-dinitrophenol (DNP) was covalently combined with a cancer receptor-binding dipeptide (IYIY) to form a dipeptide-hapten construct (IYIY-DNP, MW = 1322.33) that targets the tropomyosin receptor kinase C (TrkC)-expressed on the surface of metastatic cancer cells. IYIY-DNP facilitated selective association of RAW264.7 macrophages to the TrkC expressing 4T1 cancer cells in vitro, forming cell aggregates in the presence of anti-DNP antibodies, suggesting initiation of anti-DNP antibody-dependent cancer cell recognition of macrophages by the IYIY-DNP. In in vivo, IYIY-DNP at 10 mg/kg suppressed growth of 4T1 tumors in DNP-immunized BALB/c mice by 45% (p < 0.05), when comparing the area under the tumor growth curve to that of the saline-treated DNP-immunized mice. Meanwhile, IYIY-DNP at 10 mg/kg had no effect on TrkC-negative 67NR tumor-bearing mice immunized with DNP. Tumor growth suppression activity of IYIY-DNP in DNP-immunized mice was associated with an increase in the anti-DNP IgG (7.3 × 106 ± 1.6 U/mL) and IgM (0.9 × 106 ± 0.07 U/mL) antibodies after five cycles of DNP treatment, demonstrated potential for hapten-based pre-immunization then treatment with IYIY-DNP to elicit ADCP for improved immunotherapy of TrkC expressing cancers. [ABSTRACT FROM AUTHOR]

BODIPYs are photosensitizers activatable by light to generate highly reactive singlet oxygen (1O2) from molecular oxygen, leading to tissue damage in the photoirradiated region. Despite their extraordinary photophysical characteristics, they are not featured in clinical photodynamic therapy. This review discusses the recent advances in the design and/or modifications of BODIPYs since 2013, to improve their potential in photodynamic cancer therapy and related areas. [ABSTRACT FROM AUTHOR]

Aim: The aim of the present study was to investigate the effectiveness of transforming growth factor (TGF)-β1 antisense oligodeoxynucleotides (ODN) in ameliorating deteriorated kidney function in rats with puromycin-induced chronic renal failure (CRF). Methods: Saline, puromycin, puromycin+TGF-β1 antisense ODN or puromycin+scrambled ODN were administered to unilaterally nephrectomized rats. Renal hemodynamic and excretory measurements were taken in the anaesthetized rats that had undergone surgical procedure. Results: It was observed that in the CRF rats, there was a marked reduction in the renal blood flow (RBF), glomerular filtration rate (GFR), severe proteinuria, and almost 6-fold increased fractional excretion of sodium (FE Na+) as compared to that in the control rats (all P<0.05). It was further observed that in the CRF rats, the treatment with TGF-β1 antisense, but not scrambled ODN, markedly attenuated the reduction of RBF, GFR, and proteinuria and markedly prevented the increase of the FE Na+ (all P<0.05). In addition, the renal hypertrophy in the CRF group ( P<0.05 vs non-renal failure control) was markedly attenuated after treatment with TGF-1 antisense ODN ( P<0.05). Focal segmental glomerulosclerosis was evident only in the untreated and scrambled ODN-treated CRF groups. An interesting observation of this study was that in the CRF rats, although there was marked attenuating and preventive effects of the TGF-β1 antisense ODN on the deteriorated renal functions, the antisense treatment did not cause any marked change in the renal expression of TGF-β1 at the protein level. Conclusion: Collectively, the data obtained suggests that TGF-β1 antisense ODN possesses beneficial effects in puromycin-induced chronic renal failure and that the deterioration in morphology and impaired renal function in this pathological state is in part dependent upon the action of TGF-β1 within the kidney. [ABSTRACT FROM AUTHOR]

Tropomyosin receptor kinase C (TrkC) targeted ligand-photosensitizer construct, IYIY-diiodo-boron-dipyrromethene (IYIY-I2-BODIPY) and its scrambled counterpart YIYI-I2-BODIPY have been prepared. IYIY-I2-BODIPY binds TrkC similar to neurotrophin-3 (NT-3), and NT-3 has been reported to modulate immune responses. Moreover, it could be shown that photodynamic therapy (PDT) elevates antitumor immune responses. This prompted us to investigate the immunological impacts mediated by IYIY-I2-BODIPY in pre- and post-PDT conditions. We demonstrated that IYIY-I2-BODIPY (strong response) and YIYI-I2-BODIPY (weak response) at 10 mg/kg, but not I2-BODIPY control, increased the levels of IL-2, IL-4, IL-6 and IL-17, but decreased the levels of systemic immunoregulatory mediators TGF-β, myeloid-derived suppressor cells and regulatory T-cells. Only IYIY-I2-BODIPY enhanced the IFN-γ+ and IL-17+ T-lymphocytes, and delayed tumor growth (~20% smaller size) in mice when administrated daily for 5 days. All those effects were observed without irradiation; when irradiated (520 nm, 100 J/cm2, 160 mW/cm2) to produce PDT effects (drug-light interval 1 h), IYIY-I2-BODIPY induced stronger responses. Moreover, photoirradiated IYIY-I2-BODIPY treated mice had high levels of effector T-cells compared to controls. Adoptive transfer of immune cells from IYIY-I2-BODIPY-treated survivor mice that were photoirradiated gave significantly delayed tumor growth (~40-50% smaller size) in recipient mice. IYIY-I2-BODIPY alone and in combination with PDT modulates the immune response in such a way that tumor growth is suppressed. Unlike immunosuppressive conventional chemotherapy, IYIY-I2-BODIPY can act as an immune-stimulatory chemotherapeutic agent with potential applications in clinical cancer treatment. [ABSTRACT FROM AUTHOR]