将已构建的插入IL-24等细胞因子编码基因的溶瘤病毒，转染到体外诱导的HIM-IC细胞内，通过特殊的基因改造，使溶瘤病毒在HIM-IC细胞内增殖但不破坏HIM-IC细胞，然后向患者体内回输HIM-IC细胞，使融瘤病毒特异性导向肿瘤细胞，在其内大量复制并＊终摧毁肿瘤细胞。技术特点l   IC细胞本身具有非MHC限制性的非特异性免疫杀伤作用，对肿瘤细胞有杀伤活性；l   通过IC细胞携带溶瘤病毒并释放到肿瘤细胞内，使溶瘤病毒特异性导向肿瘤细胞，并发挥溶瘤活性；l   插入在溶瘤病毒基因组的细胞因子基因随着病毒的扩增在肿瘤细胞内表达，并释放细胞因子，直接发挥抗肿瘤活性；l   IC细胞作为载体向肿瘤细胞导向溶瘤病毒，减少溶瘤病毒直接注射被机体免疫系统的清除以及副作用； 因此这种溶瘤病毒与HIM-IC免疫细胞的联合治疗法比单一的细胞治疗或溶瘤病毒治疗具有更高的特异性和杀伤活性。Oncolytic virus / CIK technologyThe oncolytic virus integrated with IL-24 and other cytokine genes was transduced into CIK cells. The genetically modified oncolytic virus would proliferate in CIK cells without destroying CIK cells. The virus harbored CIK cells were then transfused to the patient, specifically targeting the oncolytic virus to tumor cells, and ultimately destroy the tumor cells. Technical features 1.   CIK cells possess non-MHC-specific and nonspecific cytotoxicity against tumor cells; 2.   Oncolytic virus carried in the CIK cells would be targeted to, released into and then more  efficiently kill the tumor cells;3.   The cytokine gene integrated in the genome of the oncolytic virus is expressed in the tumor cells along with the expansion of the virus, which directly develop the antitumor activity.4.   Using CIK cell as carrier of oncolytic virus helps to reduce the clearence of virus by receptorimmune system and otherwise some side effects caused by naked virus injection  Therefore, the combination of the oncolytic virus and CIK immune cells has a higher specificity and killing activity than CIK or oncolytic virus alone.

双特异性抗体是含有两种特异性抗原结合位点的双功能抗体。我们通过化学交联法将抗CD3单抗与曲妥珠单抗交联，获得了对肿瘤细胞和淋巴细胞的双向识别作用的双特异抗体。此双特异性抗体一方面通过CD3单抗识别HIM-IC细胞；另一方面，通过曲妥珠单抗识别肿瘤表面HER2受体。在HIM-IC细胞体外诱导、培养的＊后阶段加入该双特异抗体，双特异抗体即通过抗CD3抗体结合到HIM-IC细胞表面，HIM-IC细胞回输到体内后，其表面的双特异抗体将HIM-IC细胞靶向募集到肿瘤细胞表面，从而提高HIM-IC细胞对肿瘤细胞的识别和杀伤活性。技术特点l   制备技术相对简单；l   利用抗体-抗原的强大亲和力，大大提高HIM-IC细胞对肿瘤细胞的识别和杀伤机会。Bispecific antibody / DC-CIK technologyA bispecific antibody is a bifunctional antibody that contains two specific antigen binding sites. We cross-linked anti-CD3 monoclonal antibody with trastuzumab by chemical cross-linking, and obtained bi-specific antibodies for bi-directional recognition of tumor cells and lymphocytes. This bispecific antibody recognizes CIK cells via CD3 target and recognizes tumor cells via HER2 receptor. In the final stage of DC-CIK cells culturing, the bispecific antibody was added and binds to the surface of CIK cells through anti-CD3 antibody. After transfusion, the  cells were recruited to tumor cells through bispecific antibody, thereby enhancing the recognition and killing activity of CIK cells to tumor cells. Technical features1.   The preparation technique is relatively simple 2.   The strong affinity of antibody to antigen greatly improves the DC-CIK cells on tumorcell recognition and killing opportunities

我们的TCR-T技术是利用我们独特的人工抗原提成细胞技术制备肿瘤特异性的CTLs, 然后从分离得到的单个抗原肽-Tetramer阳性的CTL细胞中测定其基因顺序。运用DNA重组技术将克隆得到的高亲和性的TCRα和β链基因片段插入到逆转录病毒或慢病毒等基因转导载体中。通过不同基因转导技术将TCR基因转导至外周血T细胞，使其表达抗原特异性TCR，成为能够特异性识别肿瘤抗原的CTL，体外扩增并回输病人，达到体内杀死肿瘤细胞的作用。 我们目前选择的靶分子是NY-ESO-1，全称New York esophageal squamous cell carcinoma 1，是肿瘤-**抗原（cancer-testis antigens,  CTA）家族重要成员之一。NY-ESO-1具有诱导体液免疫应答的能力, 也具有激活CD4 +和CD8 + T淋巴细胞的能力, 是到目前为止被发现的免疫原性＊强大的肿瘤特异性抗原。NY-ESO-1在多种肿瘤细胞中都有表达，包括黑色素瘤、食道癌、膀胱癌、肺癌等。但 NY-ESO-1 在除**组织以外的正常组织不表达，**组织不表达 MHC  I 类及 II 类分子，所以不会被 T 细胞识别杀伤。正是由于这一特征，NY-ESO-1 成为了肿瘤免疫治疗研究的热点。技术特点l  保持TCR和共刺激因子相互作用的天然结构，既保留信号激活的强度，又保证了强度的控制，因而更强，更有效地激活重新编程的T细胞，也具有一定的安全性；l  高效的特异TCR克隆选择系统；l  特异TCR在CTL细胞表面的高密度表达，提高了对肿瘤特异识别和杀伤作用。TCR-T Technology    Our TCR-T technique is featured by using the patented artificial antigen presentation system to prepare tumor specific CTL cells. The sequences coding for TCRα and βsubunits are decoded and cloned from antigen peptide-Tetramer positive cells. The TCRα and β gene will then be inserted into retroviruses or lentiviruses derived vectors and transduced into peripheral blood derived T cells for high expression of antigen-specific TCR to become tumor-specific CTL clone (TCR-T) and to obtain potent tumor cell killing activity.    Currently, we are focused on target molecule NY-ESO-1 (New York esophageal squamous cell carcinoma 1), an important member of cancer-testis antigens (CTA) family. NY-ESO-1 can induce humoral immune response and activate CD4+ and CD8+ T-lymphocytes. NY-ESO-1 is widely expressed in a variety of tumor cells such as melanoma, esophageal cancer, bladder cancer, lung cancer and exhibits, thus far, strongest immunogenicity among all tumor-specific antigens. NY-ESO-1 has not been detected in normal tissues except in testicular tissue. Testis cells do not express MHC-I and MHC-II molecules, thereby escaping T cell attack via NY-ESO-1 target. This unique property makes NY-ESO-1 a hotspot in tumor immunotherapy research.Technical features1.    Maintaining the natural structure of TCR for proper interaction with cofactors, not onlymaintains the strength of activation signal, but also ensures the control of activation strength, and thus manifests safety2.    Efficient and specific system of TCR cloning and screening3.    Higher expression of specific TCR enables CTLto recognizie and kill tumor cells with more efficiency 

嵌合抗原受体T细胞（CAR-T细胞）是在体外构建一个嵌合基因，包括识别肿瘤抗原的单链抗体可变区的基因片段和T细胞激活辅助因子的基因片段,然后通过转导的方法转染患者的T细胞，即“重编码”患者的T细胞，使其表达嵌合抗原受体(CAR)。经体外培养生成大量肿瘤特异性的CAR-T细胞，回输到患者体内，达到有效识别和杀伤肿瘤细胞的目的。技术特点l  靶点不受MHC的限制；l  识别靶分子的亲和力强，有效捕捉癌细胞；l  可设计成多靶点的CAR基因，减少或者消除细胞因子释放症的副作用；l  具有免疫记忆功能。CAR-T Technology     Chimeric antigen receptors T cells (CAR-T) designates the technology that engineers receptors (usually single chain monoclonal antibody plus the sequence of T cell costimulatory domains) and expresses them on  T cells. Thus constructed CAR-T cells specifically recognize and kill tumor cells, as demonstrated in vitro and in vivo. Technical features1.    Targets are not restrained by MHC, broad-spectrum indications2.    Strong affinity to the target molecules on cancer cells, efficient killing of cancer cells in  culture or in circulating system;3.    can be designed to multiple target points and more accurate, to reduce side effects of cytokine release4.    With immune memory function