Christina To | The Chinese University of Hong Kong (original) (raw)
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Papers by Christina To
European Journal of Immunology, 2011
The concept of DC-based tumour vaccine has been tested both clinically and experimentally for the... more The concept of DC-based tumour vaccine has been tested both clinically and experimentally for the past two decades. Even though only limited success has been achieved to date, DC vaccination remains a promising immunological approach against tumours and deserves further exploration. It aims to elicit and establish specific immunity to destroy tumours. By such an approach, DC are used not only as a vector to deliver tumour antigens, but also as a ''natural adjuvant'' to boost vaccine efficacy. Tumours are however of mutated ''self'', to which the host immune system is essentially tolerated in the absence of external perturbation otherwise. Such a live cell-based approach is unfortunately extremely sensitive to, hence its efficacy inevitably limited by, the tumour microenvironment. Certain immunosuppressive mechanisms triggered by the tumour cells are therefore major obstacles against successful DC vaccination. Attempts have since been made in order to overcome these hurdles. This brief review summarises some of the earlier and current findings, and compares the effectiveness of various approaches used in these studies. It focuses particularly on strategies aimed at enhancing DC immunogenicity, through molecular modifications and functional conditioning of the cell vectors, targeting both the positive and negative regulators of DC functions. By dissecting the roles of DC in immunity versus tolerance induction, and the very mechanisms underlying autoimmunity, we examine further and try to explain how the suppressed or ''misguided'' immunity may be alternatively switched-on and more effectively redirected for cancer therapy.
European Journal of Immunology, 2005
Title character counts: 117 Total number of words in the leading paragraph (Abstract): 186 Number... more Title character counts: 117 Total number of words in the leading paragraph (Abstract): 186 Number of figures: 5 Number of references: 46 Abbreviations: DNA: deoxyribonucleic acid; Anti-dsDNA: antibody against double stranded DNA; DC: dendritic cells; Nec: necrotic cells; Apo: apoptotic cells; DC/nec: DC loaded with necrotic cells; DC/apo: DC loaded with apoptotic cells; ICs: immune complexes. Abstract Systemic lupus erythematosus (SLE) is an autoimmune disorder of a largely unknown aetiology. Anti-double stranded DNA antibodies (anti-dsDNA) are a classical hallmark of the disease, the mechanism underlying their induction remains unclear. We demonstrate here that, in lupus-prone and normal mouse strains, strong anti-dsDNA antibody responses can be induced by dendritic cells (DCs) that have ingested syngeneic necrotic (DC/nec), but not apoptotic (DC/apo), cells. Clinical manifestations of lupus were evident however only in susceptible mouse strains, which correlate with the ability of DC/nec to release IFN-γ and to induce the pathogenic IgG2a anti-dsDNA antibodies. Injection of DC/nec not only accelerated disease progression in the MRL/MpJ-lpr/lpr lupusprone mice but also induced a lupus-like disease in the MRL/MpJ-+/+ wild-type control strain. Immune complex deposition was readily detectable in the kidneys, and the mice developed proteinuria. Strikingly, female MRL/MpJ-+/+ mice that had received DC/nec, but not DC/apo, developed a 'butterfly' facial lesion resembling a cardinal feature of human SLE. Our study therefore demonstrates that DC/nec inducing a Th1 type of responses, which are otherwise tightly regulated in a normal immune system, may play a pivotal role in SLE pathogenesis.
Aim: Oral treatment with asunaprevir and daclatasvir has been reported to yield a SVR ratio of 80... more Aim: Oral treatment with asunaprevir and daclatasvir has been reported to yield a SVR ratio of 80% in patients with genotype 1b HCV infection, however, treatment failure has been reported, especially in patients with HCV strains showing the NS5A-Y93H mutation at baseline. An assay system to detect such strains was established to facilitate selection of appropriate candidates for this antiviral therapy.
European Journal of Immunology, 2011
The concept of DC-based tumour vaccine has been tested both clinically and experimentally for the... more The concept of DC-based tumour vaccine has been tested both clinically and experimentally for the past two decades. Even though only limited success has been achieved to date, DC vaccination remains a promising immunological approach against tumours and deserves further exploration. It aims to elicit and establish specific immunity to destroy tumours. By such an approach, DC are used not only as a vector to deliver tumour antigens, but also as a ''natural adjuvant'' to boost vaccine efficacy. Tumours are however of mutated ''self'', to which the host immune system is essentially tolerated in the absence of external perturbation otherwise. Such a live cell-based approach is unfortunately extremely sensitive to, hence its efficacy inevitably limited by, the tumour microenvironment. Certain immunosuppressive mechanisms triggered by the tumour cells are therefore major obstacles against successful DC vaccination. Attempts have since been made in order to overcome these hurdles. This brief review summarises some of the earlier and current findings, and compares the effectiveness of various approaches used in these studies. It focuses particularly on strategies aimed at enhancing DC immunogenicity, through molecular modifications and functional conditioning of the cell vectors, targeting both the positive and negative regulators of DC functions. By dissecting the roles of DC in immunity versus tolerance induction, and the very mechanisms underlying autoimmunity, we examine further and try to explain how the suppressed or ''misguided'' immunity may be alternatively switched-on and more effectively redirected for cancer therapy.
European Journal of Immunology, 2005
Title character counts: 117 Total number of words in the leading paragraph (Abstract): 186 Number... more Title character counts: 117 Total number of words in the leading paragraph (Abstract): 186 Number of figures: 5 Number of references: 46 Abbreviations: DNA: deoxyribonucleic acid; Anti-dsDNA: antibody against double stranded DNA; DC: dendritic cells; Nec: necrotic cells; Apo: apoptotic cells; DC/nec: DC loaded with necrotic cells; DC/apo: DC loaded with apoptotic cells; ICs: immune complexes. Abstract Systemic lupus erythematosus (SLE) is an autoimmune disorder of a largely unknown aetiology. Anti-double stranded DNA antibodies (anti-dsDNA) are a classical hallmark of the disease, the mechanism underlying their induction remains unclear. We demonstrate here that, in lupus-prone and normal mouse strains, strong anti-dsDNA antibody responses can be induced by dendritic cells (DCs) that have ingested syngeneic necrotic (DC/nec), but not apoptotic (DC/apo), cells. Clinical manifestations of lupus were evident however only in susceptible mouse strains, which correlate with the ability of DC/nec to release IFN-γ and to induce the pathogenic IgG2a anti-dsDNA antibodies. Injection of DC/nec not only accelerated disease progression in the MRL/MpJ-lpr/lpr lupusprone mice but also induced a lupus-like disease in the MRL/MpJ-+/+ wild-type control strain. Immune complex deposition was readily detectable in the kidneys, and the mice developed proteinuria. Strikingly, female MRL/MpJ-+/+ mice that had received DC/nec, but not DC/apo, developed a 'butterfly' facial lesion resembling a cardinal feature of human SLE. Our study therefore demonstrates that DC/nec inducing a Th1 type of responses, which are otherwise tightly regulated in a normal immune system, may play a pivotal role in SLE pathogenesis.
Aim: Oral treatment with asunaprevir and daclatasvir has been reported to yield a SVR ratio of 80... more Aim: Oral treatment with asunaprevir and daclatasvir has been reported to yield a SVR ratio of 80% in patients with genotype 1b HCV infection, however, treatment failure has been reported, especially in patients with HCV strains showing the NS5A-Y93H mutation at baseline. An assay system to detect such strains was established to facilitate selection of appropriate candidates for this antiviral therapy.