生物谷將于5月17日到18日在上海舉辦2018（第九屆）細(xì)胞治療國際研討會，本次會議設(shè)置主論壇、細(xì)胞治療學(xué)術(shù)專場、細(xì)胞治療臨床研究專場，細(xì)胞治療產(chǎn)業(yè)論壇以及細(xì)胞治療投融資對接。 會議將力求推動臨床研究與細(xì)胞治療的產(chǎn)業(yè)化進(jìn)程， 邀請國內(nèi)外頂尖的細(xì)胞治療基礎(chǔ)研究和臨床專家、業(yè)內(nèi)行家以及藥物評審專家， 瞄準(zhǔn)細(xì)胞治療研究的最新研究動態(tài)和進(jìn)展，針對細(xì)胞治療的臨床監(jiān)管、治療規(guī)范、細(xì)胞治療安全性，新型CAR-T、CAR-NK、TCR-T療法、實體瘤治療、腫瘤免疫檢查點抑制劑、間充質(zhì)干細(xì)胞臨床應(yīng)用、細(xì)胞制備的自動化技術(shù)、基因編輯與細(xì)胞治療、腫瘤免疫治療的伴隨診斷等熱門議題進(jìn)行討論。

會議官網(wǎng)：http://meeting.世聯(lián)博研Bioexcellence/2018cell-therapies

截止今天，嘉賓已確認(rèn)了大半，今天小編為大家準(zhǔn)備了8位嘉賓的演講摘要，讓各位老師一睹為快！如果覺得還不錯，那就趕快報名吧！

劉東方 Assistant Professor Houston Methodist Research Institute

演講題目：快速有效預(yù)測CAR-T/NK療效及副作用

演講摘要：準(zhǔn)確迅速地預(yù)測CAR T/NK細(xì)胞治療的臨床效能及其毒副作用是當(dāng)今免疫細(xì)胞治療中未解決的關(guān)鍵問題之一。目前，沒有任何一個單一參數(shù)可以精準(zhǔn)有效地預(yù)測CAR T/NK的臨床療效及其可能存在的毒副作用。隨著免疫細(xì)胞治療的高速發(fā)展，我們可以推測臨床醫(yī)生在選擇不同藥企相似的CAR T/NK細(xì)胞產(chǎn)品時將面臨困境。 醫(yī)療市場缺乏高通量并排評估不同藥企相似的CAR T/NK細(xì)胞產(chǎn)品對同一適應(yīng)癥病人的臨床效能及其毒副作用。 該研究中，我們通過高通量，定量檢測CAR T/NK免疫突觸的質(zhì)量來預(yù)測其臨床效能和毒副作用。該技術(shù)，可能為免疫細(xì)胞的個體化，精準(zhǔn)治療引入新的臨床檢測指標(biāo)及新的預(yù)測工具。

龐希寧 教授 中國醫(yī)科大學(xué)基礎(chǔ)醫(yī)學(xué)院

演講題目：人羊膜干細(xì)胞旁分泌作用促進(jìn)皮膚組織再生機制的研究

演講摘要：移植干細(xì)胞促進(jìn)組織修復(fù)，除了其分化為所修復(fù)組織的細(xì)胞外，也許更重要的方式是干細(xì)胞的旁分泌作用改善受損組織的微環(huán)境，啟動組織自身干細(xì)胞增殖和分化來修復(fù)損傷。已有研究表明干細(xì)胞可產(chǎn)生微泡，其內(nèi)含有各種活性蛋白因子、還可以含有mRNA、miRNA甚至線粒體等細(xì)胞器。這將對損傷組織微環(huán)境產(chǎn)生非常大的影響。人羊膜干細(xì)胞包括羊膜間充質(zhì)干細(xì)胞和羊膜上皮干細(xì)胞，人羊膜干細(xì)胞是最具活力的干細(xì)胞之一，具有很強的增殖能力和分化潛能，還具有很強的旁分泌能力。人羊膜干細(xì)胞的移植將會明顯影響損傷組織的微環(huán)境，促進(jìn)受損組織的修復(fù)。我們對人羊膜干細(xì)胞進(jìn)行了mRNA和miRNA測序，分析了其可能產(chǎn)生的旁分泌活性蛋白質(zhì)，并通過搜集含有其旁分泌產(chǎn)物的培養(yǎng)液，分別作用于皮膚角質(zhì)形成細(xì)胞、皮膚成纖維細(xì)胞和血管內(nèi)皮細(xì)胞，研究其旁分泌作用對它們的影響。發(fā)現(xiàn)其旁分泌產(chǎn)物能不同程度的促進(jìn)這些細(xì)胞的增殖、遷移和分化，并研究了產(chǎn)生這些作用的主要分子，用這些分子在體外作用于皮膚角質(zhì)形成細(xì)胞、皮膚成纖維細(xì)胞和血管內(nèi)皮細(xì)胞，進(jìn)行進(jìn)一步的研究，同時通過動物實驗在整體水平進(jìn)行研究，深入探討羊膜干細(xì)胞旁分泌作用促進(jìn)皮膚再生的分子機理。期望以后能通過這些分子直接改善受損組織的微環(huán)境，促進(jìn)組織的再生，達(dá)到治療皮膚損傷的目的。

李光申 講座教授/副總院長 陽明大學(xué)臨床醫(yī)學(xué)研究所/臺北市立聯(lián)合醫(yī)院

演講題目： Research and application of mesenchymal stem cells: My 20-Year Journey

演講摘要：Mesenchymal stem cells (MSCs) were first defined as a group of cells which were of self-renewal ability, were able to be culture-expanded for a prolonged period of time, and are able to differentiate into various lineages of connective progenies originated from embryonic mesoderm including bone, cartilage and adipose tissues. These cells were first isolated from bone marrow; subsequently, MSCs isolated from other sources such as liposuction fat, synovial tissues and trabecular bone have been reported by other investigators. Recently, it was reported that certain population of stem cells in human bone marrow, although low in frequency, were able to differentiate into cells and tissues originated from not only mesoderm, but also ectoderm.          

In our laboratory, we have successfully isolated and culture-expanded MSCs from human bone marrow and umbilical cord blood using negative immuno-selection and limiting dilution methods. Surface phenotype of these cells was performed using flow cytometry and surface marker phenotype was characteristic of MSCs. These MSCs were able to differentiate into progenies originated from all three germ layers including osteoblasts, chondrocytes, adipocytes, neuroglial cells and hepatocytes. In vitro functionality of these differentiated progenies was also demonstrated. Particularly, MSC-differentiated hepatocytes have been shown to be able to secrete urea and uptake of low density lipoproteins is also noted in these MSC-differentiated hepatocytes.

There are various applications of MSCs in biomedical research both in vitro and in vivo. The in vitro model of MSC culture can serve as an excellent model to study the control of differentiation as well as the cell fate in each lineage. Novel genes and proteins that control differentiation can also be explored in this model. Besides, it can also be used for screening of new drugs and compounds. Most important of all, MSCs are indispensable in the study of cell therapy, tissue engineering and regenerative medicine.

Over the years, we have published more than one hundred peer-reviewed research articles to report our findings regarding the molecular mechanisms that govern the fate choice and differentiation, as well as the plasticity andapplications of MSCs. In particular, our efforts made to elucidate how MSCs sense and respond to biophysical and mechanical stimuli have substantially contributed to the understanding of mechanobiology in MSCs.

In summary, it is foreseeable that in the near future, MSCs will revolutionize the treatment of a variety of diseases. Therefore, more efforts should be made to further elucidate the basic science of MSCs to accelerate their clinical translation from bench to bedside.

趙陽兵 教授/主任 美國賓夕法尼亞大學(xué)醫(yī)學(xué)院Abramson 腫瘤中心T細(xì)胞工程實驗室

演講題目：Use CRISPR Gene Editing To Improve CAR-T/TCR-T Adoptive Immunotherapy For Cancers （CRISPR/CAS9技術(shù)用于促進(jìn)腫瘤CAR-T/TCR-T細(xì)胞的過繼性免疫治療）

演講摘要：CAR-T 治療白血病和淋巴瘤已進(jìn)入商業(yè)化進(jìn)程。然而，不同于血液系統(tǒng)腫瘤，實體腫瘤的免疫治療更為復(fù)雜，難度更高，并且需研發(fā)新的技術(shù)攻克。CAR-T /TCR-T 治療實體腫瘤需多方面的突破， 尤其是靶的特異性， 克服腫瘤微環(huán)境的抑制及提高T細(xì)胞本身的質(zhì)量?；蚓庉嫾夹g(shù)，尤其是CRISPR/CAS9簡單高效基因編輯技術(shù)的高速發(fā)展，對CAR-T/TCR-T攻克實體瘤提供了廣泛的應(yīng)用前景。本報告介紹了如何通過應(yīng)用CRISPR/CAS9基因編輯技術(shù)對CART或TCR-T進(jìn)行改造來制備通用型或功能增強型CAR-T或TCR-T并用于臨床。我們發(fā)現(xiàn)， 敲除內(nèi)源性TCR的TCR-T在體外實驗或小鼠腫瘤模型中，可以達(dá)到和親和力增強型TCR一樣好的效果而不用擔(dān)心脫靶副作用。同時，應(yīng)用不同的小鼠腫瘤模型，通過應(yīng)用CRISPR/CAS9基因編輯技術(shù)敲除免疫檢查點分子PD1, CTLA4和Tim-3可明確增強CART或TCR-T療效，尤其把PD1-CD28轉(zhuǎn)換分子與Tim-3敲除同時應(yīng)用。通過復(fù)雜的T細(xì)胞修飾，有望對腫瘤過繼性免疫治療有突破性進(jìn)展。帶PD1-CD28轉(zhuǎn)換分子的Tim-3敲除的TCR-T細(xì)胞不但可以抵制腫瘤誘導(dǎo)的T細(xì)胞功能低下，在體外還可抵抗TGFb，Adenosine和抑制性T細(xì)胞（Treg）的抑制作用。

李宗海 研究員 上海市腫瘤研究所

演講題目：針對實體瘤微環(huán)境的下一代CAR-T的研究與開發(fā)

演講摘要：實體瘤惡劣微環(huán)境是嚴(yán)重影響CAR-T細(xì)胞免疫治療存活及發(fā)揮功能的重要原因，因此如何由針對性第開發(fā)出一些高效能夠克服這些微環(huán)境的技術(shù)，甚至把這些不利因素變成有利因素，無疑是下一代CAR-T開發(fā)的重點，我將介紹一下國內(nèi)外特別是我們團隊發(fā)展的一些CAR-T新技術(shù)。

Li Zhou VP of Cell Engineering TxCell

TOPIC: Developing CAR Treg for Treating Autoimmune Disease

SUMMARY:The recent FDA approvals of the first two CAR T cell treatments for blood cancers (Kymriah? and Yescarta?) mark the beginning of a new era. This is a fast progressing area. We can expect that there will be continuation of success on CAR-T in the blood cancers with reduced toxicity, reduced rate of relapse etc. There will be breakthrough on solid tumors by the CAR-T therapy, and off-the-shelf treatment will become a reality. In addition, the technology of genetically modified T cells will move beyond oncology. The Development of CAR-Treg cell therapy to target autoimmune diseases and induction of tolerance will likely be the next wave. At TxCell, we are developing CAR Treg for autoimmune disease and organ transplant rejection. HLA A2 appears to be an ideal target for organ transplant rejection, as HLAs are membrane-bound protein specifically expressed on the transplanted tissues, HLA A2 expression level is high, it can robustly induce CAR-Treg activity. It has high allelic frequency--about 25% transplanted organs are HLA A2 mismatched in North America. We are developing HLA A2 CAR-Treg therapy for organ transplant rejection and will start the first ever clinical trial using CAR-Treg cells. We have shown that HLA A2 CAR-Treg cells can prevent GVHD in a mouse model. Other proof of concept data will also be presented.

譚文松 教授/董事長  華東理工大學(xué)/生物反應(yīng)器工程國家重點實驗室/上海倍諳基生物科技有限公司

演講題目：干細(xì)胞/免疫效應(yīng)細(xì)胞規(guī)?；苽潢P(guān)鍵技術(shù)

演講摘要：高效、經(jīng)濟、快速實現(xiàn)干細(xì)胞/免疫效應(yīng)細(xì)胞的體外擴增，建立基于生物反應(yīng)器平臺的規(guī)?；詣踊委熂壖?xì)胞產(chǎn)品制備工藝過程，獲得高品質(zhì)的細(xì)胞產(chǎn)品是細(xì)胞治療產(chǎn)業(yè)發(fā)展的核心技術(shù)之一。本團隊以造血干細(xì)胞、間充質(zhì)干細(xì)胞以及免疫效應(yīng)細(xì)胞為對象，通過研究體外培養(yǎng)過程中細(xì)胞的物質(zhì)和能量代謝特性，以及深入解析體外培養(yǎng)過程中細(xì)胞擴增、營養(yǎng)物質(zhì)消耗、代謝產(chǎn)物生成的動力學(xué)特性以及主要代謝途徑關(guān)鍵酶活性的動態(tài)變化規(guī)律，設(shè)計開發(fā)能夠促進(jìn)細(xì)胞增殖、調(diào)控細(xì)胞功能的無血清培養(yǎng)基組成，并進(jìn)一步采用蛋白固載、包埋緩釋等技術(shù)，優(yōu)化細(xì)胞因子的作用方式，實現(xiàn)效應(yīng)細(xì)胞的高效擴增。最后，結(jié)合生物反應(yīng)器的優(yōu)化設(shè)計和操作，建立了規(guī)?；母杉?xì)胞/免疫效應(yīng)細(xì)胞高效擴增技術(shù)，為解決細(xì)胞治療面臨的細(xì)胞數(shù)量不足和質(zhì)量難以保證等瓶頸問題、加快其臨床應(yīng)用和產(chǎn)業(yè)化步伐奠定了基礎(chǔ)。

楊林 教授 蘇州大學(xué)唐仲英血液學(xué)研究中心/博生吉醫(yī)藥科技（蘇州）有限公司董事長兼首席科學(xué)官

演講題目：全自動、全封閉CAR-T細(xì)胞的制備工藝探討

演講摘要：CAR-T細(xì)胞治療在血液惡性腫瘤的臨床試驗中表現(xiàn)出了巨大的潛力。但是T細(xì)胞的體外基因修飾涉及到諸多步驟，尤其是在新藥監(jiān)管模式的要求下，要在GMP條件下制備出合格的CAR-T細(xì)胞、而且這樣的制備工藝還必須能滿足未來產(chǎn)業(yè)化的要求，就成為了一個CAR-T細(xì)胞發(fā)展中必須克服的障礙。

國家食品藥品監(jiān)督管理總局藥品審評中心近日發(fā)布了關(guān)于《細(xì)胞制品研究與評價技術(shù)指導(dǎo)原則》（試行版），不僅正式明確了CAR-T細(xì)胞按照藥品評審原則監(jiān)管，而且在制備工藝上明確指出了“全封閉、全自動”的發(fā)展要求。楊林博士將針對CAR-T細(xì)胞的工業(yè)制備，結(jié)合自身的發(fā)展經(jīng)驗，進(jìn)行系統(tǒng)闡述和比較，為CAR-T細(xì)胞產(chǎn)業(yè)的工業(yè)化發(fā)展，指明方向。