• 제목/요약/키워드: Antibody therapy

검색결과 225건 처리시간 0.028초

A Novel Anti-PD-L1 Antibody Exhibits Antitumor Effects on Multiple Myeloma in Murine Models via Antibody-Dependent Cellular Cytotoxicity

  • Ahn, Jae-Hee;Lee, Byung-Hyun;Kim, Seong-Eun;Kwon, Bo-Eun;Jeong, Hyunjin;Choi, Jong Rip;Kim, Min Jung;Park, Yong;Kim, Byung Soo;Kim, Dae Hee;Ko, Hyun-Jeong
    • Biomolecules & Therapeutics
    • /
    • 제29권2호
    • /
    • pp.166-174
    • /
    • 2021
  • Multiple myeloma is a malignant cancer of plasma cells. Despite recent progress with immunomodulatory drugs and proteasome inhibitors, it remains an incurable disease that requires other strategies to overcome its recurrence and non-response. Based on the high expression levels of programmed death-ligand 1 (PD-L1) in human multiple myeloma isolated from bone marrow and the murine myeloma cell lines, NS-1 and MOPC-315, we propose PD-L1 molecule as a target of anti-multiple myeloma therapy. We developed a novel anti-PD-L1 antibody containing a murine immunoglobulin G subclass 2a (IgG2a) fragment crystallizable (Fc) domain that can induce antibody-dependent cellular cytotoxicity. The newly developed anti-PD-L1 antibody showed significant antitumor effects against multiple myeloma in mice subcutaneously, intraperitoneally, or intravenously inoculated with NS-1 and MOPC-315 cells. The anti-PD-L1 effects on multiple myeloma may be related to a decrease in the immunosuppressive myeloid-derived suppressor cells (MDSCs), but there were no changes in the splenic MDSCs after combined treatment with lenalidomide and the anti-PD-L1 antibody. Interestingly, the newly developed anti-PD-L1 antibody can induce antibody-dependent cellular cytotoxicity in the myeloma cells, which differs from the existing anti-PD-L1 antibodies. Collectively, we have developed a new anti-PD-L1 antibody that binds to mouse and human PD-L1 and demonstrated the antitumor effects of the antibody in several syngeneic murine myeloma models. Thus, PD-L1 is a promising target to treat multiple myeloma, and the novel anti-PD-L1 antibody may be an effective anti-myeloma drug via antibody-dependent cellular cytotoxicity effects.

신이식 후 면역반응의 이해 2부 이식면역검사와 면역억제제 (Allograft Immune Reaction of Kidney Transp lantation Part 2. Immunosuppression and Methods to Assess Alloimmunity)

  • 강희경
    • Childhood Kidney Diseases
    • /
    • 제12권2호
    • /
    • pp.133-142
    • /
    • 2008
  • 이식을 위해서는 수여자와 공여자의 혈액형과 HLA type을 알아야 한다. 통상 ABO 혈액형이 적합한 경우 이식할 수 있으며 HLA 부적합은 근래 큰 문제가 되지 않으나 HLA 부적합이 없는 경우 이식장기의 장기생존률이 높다. PRA(panel reactive antibody)는 수여자가 HLA에 감작되었는지 검사하는 방법이며 이식 전에는 반드시 교차반응 검사를 하여 음성인 경우에만 이식을 진행한다. 이식 전후에 donor specific antibody(DSA)를 검사하여 이식장기에 대한 수여자의 면역반응을 예측 할 수 있다. 근래에는 스테로이드, calcineurin inhibitor(cyclosporine, tacrolimus), azathioprine 또는 mycophenolate mofetil (MMF)의 삼제요법을 주로 사용하며 항림프구 항체 (Thymoglobulin 또는 항IL-2 receptor 항체 basiliximab/daclizumab)을 이용하여 이식 초기에 면역억제상태를 induction하는 경우도 많다.

뇌졸중 유발 백서모델에서 환경강화와 말초신경전기자극이 중추신경계의 신경성장인자에 미치는 영향 (The Effects of Nerve Growth Factor Expression of Central Nerve System by Environmental Enrichment and Peripheral Nerve Electrical Stimulation in Brain Ischemia Model Rats)

  • 김사열;김은정;김계엽
    • The Journal of Korean Physical Therapy
    • /
    • 제19권4호
    • /
    • pp.33-41
    • /
    • 2007
  • Purpose: To investigate environmental enrichment and nerve stimulation follows in application times with the change of BDNF & Trk-B receptor in the motor cortex and spinal cord. Methods: Experimental groups were divided into the five groups. Group I: normal control group, Group II: experiment control group, Group III: sciatic never electrical stimulation after MCAO, Group IV: application of only environmental enrichment after MCAO, Group V: never electrical stimulation with environmental enrichment after MCAO. Histologic observation and coronal sections were processed individually in goat polyclonal antibody phosphorylated BDNF and rabbit polyclonal antibody Trk-B receptor. Results: In immunohistochemistric response of BDNF and Trk-B, group II were showed that lower response effect at postischemic 1 days, 3 days, and 7 days. Group V were showed that increase response effect at postischemic 3 days, 7 days and 14 days. Specially showed that the most response effect at postischemic 14 days. In neurobehavioral assessment, group V were significantly difference from other groups on between-subject effects. Conclusion: The above results suggest that combined environmental enrichment with peripheral nerve electrical stimulation in focal ischemic brain injury were more improved that the change of BDNF & Trk-B receptor expression than non treatment.

  • PDF

방사면역치료(II): 임상적 이용 (Radioimmunotherapy (II): Clinical Application)

  • 천기정;강혜진;임상무
    • Nuclear Medicine and Molecular Imaging
    • /
    • 제40권2호
    • /
    • pp.74-81
    • /
    • 2006
  • Molecular targeting may be defined as the specific concentration of a diagnostic or therapeutic tracer by its Interaction with a molecular species that is distinctly present or absent in a disease state. Monoclonal antibody (mAb) is one of the successful agents for targeted therapy in cancer. To enhance the therapeutic effect, the concept of targeting radionuclides to tumors using radiolabeled mAbs against tumor-associated antigens, radioimmunotherapy, was proposed. The efficacy of radioimmunotherapy, however, has to be further optimized. Several strategies to improve targeting of tumors with radiolabeled mAbs have been developed, such as the use of mAb fragments, the use of high-affinity mAbs, the use of labeling techniques that are stable in vivo, active removal of the radiolabeled mAb from the circulation, and pretargeting strategies. Until now, however, there are many kinds of obstacles to be solved in the use of mAb for the targeted therapy. Major technical challenges to molecular targeting are related to the rapid and specific delivery of tracers to the target, the elimination of unwanted background activity, and the development of more specific targets to create a cytocidal effect. further development of this field will be determined by success in solving these challenges.

Development of Bispecific Antibody for Cancer Immunotherapy: Focus on T Cell Engaging Antibody

  • Dain Moon;Nara Tae;Yunji Park;Seung-Woo Lee;Dae Hee Kim
    • IMMUNE NETWORK
    • /
    • 제22권1호
    • /
    • pp.4.1-4.22
    • /
    • 2022
  • In the era of immunotherapeutic control of cancers, many advances in biotechnology, especially in Ab engineering, have provided multiple new candidates as therapeutic immuno-oncology modalities. Bispecific Abs (BsAbs) that recognize 2 different antigens in one molecule are promising drug candidates and have inspired an upsurge in research in both academia and the pharmaceutical industry. Among several BsAbs, T cell engaging BsAb (TCEB), a new class of therapeutic agents designed to simultaneously bind to T cells and tumor cells via tumor cell specific antigens in immunotherapy, is the most promising BsAb. Herein, we are providing an overview of the current status of the development of TCEBs. The diverse formats and characteristics of TCEBs, in addition to the functional mechanisms of BsAbs are discussed. Several aspects of a new TCEB-Blinatumomab-are reviewed, including the current clinical data, challenges of patient treatment, drawbacks regarding toxicities, and resistance of TCEB therapy. Development of the next generation of TCEBs is also discussed in addition to the comparison of TCEB with current chimeric antigen receptor-T therapy.

Seroconversion rates in kidney transplant recipients following SARS-CoV-2 vaccination and its association with immunosuppressive agents: a systematic review and meta-analysis

  • Maria Riastuti Iryaningrum;Alius Cahyadi;Fachreza Aryo Damara;Ria Bandiara;Maruhum Bonar Hasiholan Marbun
    • Clinical and Experimental Vaccine Research
    • /
    • 제12권1호
    • /
    • pp.13-24
    • /
    • 2023
  • This systematic and meta-analysis aims to evaluate humoral and cellular responses to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine among kidney transplant recipients (KTRs). We conducted a systematic literature search across databases to evaluate seroconversion and cellular response rates in KTRs receiving SARS-CoV-2 vaccines. We extracted studies that assessed seroconversion rates described as the presence of antibody de novo positivity in KTRs following SARS-CoV-2 vaccination published up to January 23rd, 2022. We also performed meta-regression based on immunosuppression therapy used. A total of 44 studies involving 5,892 KTRs were included in this meta-analysis. The overall seroconversion rate following complete dose of vaccines was 39.2% (95% confidence interval [CI], 33.3%-45.3%) and cellular response rate was 41.6% (95% CI, 30.0%-53.6%). Meta-regression revealed that low antibody response rate was significantly associated with the high prevalence of mycophenolate mofetil/mycophenolic acid (p=0.04), belatacept (p=0.02), and antiCD25 induction therapy uses (p=0.04). Conversely, tacrolimus use was associated with higher antibody response (p=0.01). This meta-analysis suggests that postvaccination seroconversion and cellular response rates in KTRs are still low. And seroconversion rate was correlated with the type of immunosuppressive agent and induction therapy used. Additional doses of the SARS-CoV-2 vaccine for this population using a different type of vaccine are considered.

Long-Term Acceptance of Fully Mhc-Mismatched Limb Allografts after a Short Course of Anti-${\alpha}{\beta}$-T Cell Receptor Monoclonal Antibody and FK506

  • Kanatani, Takako;Fujioka, H.;Lanzetta, M.;Kurosaka, M.;Matsumoto, T.;Bishop, G.A.
    • Archives of Reconstructive Microsurgery
    • /
    • 제18권1호
    • /
    • pp.9-15
    • /
    • 2009
  • Whether a seven days course of anti-${\alpha}{\beta}$-T cell receptor-antibody (${\alpha}{\beta}$-TCRmAb) combined with FK506 therapy promotes survival of limb allografts in fully MHC-mismatched combination (Brown Norway $\rightarrow$ Lewis) was examined. Eight animals received 250 ${\mu}g$/kg/day of ${\alpha}{\beta}$-TCRmAb for 7 days and 2 mg/kg/day of FK506 postoperatively (Combination therapy group). Eight animals had FK506 only (Mono-therapy group) and five animals did not have treatment (Control group). Clinical signs of early rejection with edema or erythema in the skin occurred at an average of 8.6${\pm}$1.5 days postoperatively in Control group and 59.0${\pm}$8.3 days in Mono-therapy group, both of which proceeded to irreversible rejection with necrosis of the epidermis and finally mummification. In Combination therapy group, all animals showed evidence of early rejection at an average of 56.8${\pm}$12.6 days postoperatively, however, in 4 of 8 limbs, early rejection resolved without any treatment and limbs survived >1 year. At 9 months postoperatively, donor skin grafts were accepted and third-party skin grafts were rejected by all four survivors, demonstrating donor-specific tolerance. Little or no detectable chimerism was observed in any of the 4 surviving animals at one-year postoperatively. Combination therapy of ${\alpha}{\beta}$-TCRmAb and FK506 resulted in long-term survival in fully MHC-mismatched limb transplants.

  • PDF

승모판에서 증식증(vegetation)이 확인된 원발성 항인지질 항체 증후군 1례 (A Case of Primary Antiphospholipid Antibody Syndrome Showing Vegetation on the Mitral Valve Through Echocardiography)

  • 이승엽;박승권;윤성환;정윤석;김현직;임성환;하정상;김욱년
    • Journal of Yeungnam Medical Science
    • /
    • 제15권2호
    • /
    • pp.350-358
    • /
    • 1998
  • Antiphospholipid antibody syndrome(APS) is a well-known clinical syndrome characterized by recurrent arterial or venous thromboses, recurrent fetal loss, thrombocytopenia, together with high titers of sustained anticardiolipin antibody(aCL) or lupus anticoagulant(LA). Although systemic lupus erythematosus(SLB) and APS may coexist, a high proportion of patients manifesting the APS do not suffer from classical lupus or other connective tissue disease. The patient has been defined as having a primary antiphospholipid antibody syndrome. We experienced one case of primary APS with recurrent fetal loss, recurrent cerebral infarctions, positive anticardiolipin antibody IgG and fluttering vegetation on the mitral valve, without other connective tissue diseases including SLE. Forty-three old female had 2 out of 11 criteria for the diagnosis of SLE, such as thrombocytopenia and positive antinuclear antibody, but did not meet whole criteria. The patient was treated with ticlopidine, and anticoagulant therapy was recommended.

  • PDF