《肿瘤瞭望》：免疫治疗已经成为当前淋巴瘤治疗的一个新方向，您能否对当前免疫治疗淋巴瘤的新手段进行描述概括？

 

　　Levy教授：免疫系统有多种攻击肿瘤细胞的途径，人们正在这些不同的作用机制中试图提高免疫系统的抗肿瘤作用。其中，细胞免疫治疗（嵌合抗原受体T细胞，简称CAR-T）通过使T细胞携带可识别肿瘤细胞的受体，从而定向攻击肿瘤细胞是一个重要途径。这些T细胞可从患者的血液中获得，使其携带可表达特特性识别肿瘤细胞受体的基因，并通过细胞培养获得富集的功能性T细胞。再将这些T细胞输回给患者，从而定向识别体内的肿瘤细胞并将其摧毁。另一个更加有前景的作用途径是肿瘤抗体药物，它运用全人源性抗体，使体内的T细胞重新靶向肿瘤细胞，目前关于肿瘤抗体药物的研究目前已经全面铺开。由于肿瘤细胞可通过免疫调节逃避T细胞的杀伤作用，因此新抗体能将肿瘤细胞的免疫调节作用抑制，从而使T细胞实现对肿瘤细胞的清剿。相比前一种需要针对不同患者的特异性T细胞基因，它将是一种可适用于所有肿瘤患者的治疗策略。

 

　　《肿瘤瞭望》：针对免疫细胞表面抗原CD19的嵌合抗原受体CAR-T治疗是当前最新进展且前景光明的治疗策略，那么CAR-T在治疗复发难治淋巴瘤中的地位和疗效如何？

 

　　Levy教授：迄今为止，CAR-T细胞治疗设计出了针对CD19这一肿瘤抗原的嵌合型抗体。CD-19是多种淋巴瘤包括非霍奇金氏淋巴瘤、急性淋巴细胞白血病的靶向抗原。目前的研究表明CAR-T细胞治疗在一些白血病和淋巴瘤患者中有较好的疗效，但是它不是对所有患者有效。

 

　　《肿瘤瞭望》：诸如PD1在内针对宿主免疫系统的PD-1已经迅速地改变了淋巴瘤治疗现状，那么PD-1对于复发难治患者治疗的效果如何？

 

　　Levy教授：PD-1对于复发难治的霍奇金淋巴瘤患者治疗应答率高达80%，在本届Lugano国际淋巴瘤大会上，我们将了解到关于PD-1治疗复发难治的霍奇金淋巴瘤患者应答可持续时间的研究，相信会给我们带来很好的结果。目前，每年将近有一半的患者面临着肿瘤复发的问题，PD-1的应用将很大程度改善患者的生存。

 

　　《肿瘤瞭望》：靶向治疗与化疗药物联合是在一线治疗中十分具有前景，您是如何看待这种联合治疗方案的临床应用的？

 

　　Levy教授：关于靶向治疗与化疗药物联合的运用，目前尚未在治疗中获得足够的验证，本届大会上我们也将看到更多的有关于这个话题的研究数据。我们都期待着最佳的联合治疗方案。鉴于PD-1在一些患者中证实具有很好的治疗应答，我们期待基于PD-1的联合治疗将使更多的患者获益。目前关于联合治疗有很多好的想法，然而一些获得的结果不算理想，我们还需要从中汲取经验、不断学习。

 

　　《肿瘤瞭望》：目前的趋势是小分子药物联合免疫治疗有可能在不引起目前化疗毒副反应的情况下治愈癌症，您是如何看待这种趋势在淋巴瘤治疗中的应用前景的？

 

　　Levy教授：个人认为小分子药物联合免疫治疗将是未来肿瘤治疗的方向。我们所说的找到正确联合方案，不仅仅意味着疗效更好，而且也意味着不良反应更少。现实中，这是非常棘手的难题，因为联合治疗对于肿瘤具有更多的杀伤力，同时它们也将对于人体正常组织具有影响。因此，我们需要处理好疗效与不良反应之间的矛盾关系，在努力将联合治疗的疗效提高的同时，降低治疗的不良反应。

 

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　　Q1: Immunotherapy is now one of the mainstays of treatment for lymphoma. Could you make a description of the current newer versions of immune system therapies for lymphomas?

 

　　Dr Levy: The immune system has different ways of attacking cancer cells and we are trying to enhance each of these different ways. One of those is making T cells that have a new receptor that recognizes a target on the cancer cell. These T cells can be made from the person’s blood by placing a new gene in the T cells， producing large numbers of the cells， then giving them back to the patient. These then find and target the tumor and destroy it. An even more exciting way is the use of new antibodies that break away from the immune system and teach already existing T cells in the body to target cancer cells. We are already trying to do this， but the cancer cells are making checkpoint molecules that tell the T cells not to kill， so these antibodies are now inhibiting the checkpoint molecules so the T cells already in the body can kill. This is a treatment we can make with the same antibody for everyone and we don’t need to make a specialized T cell gene for each individual person.

 

　　Q2: Engineered T cell that carries a receptor incorporating the recognition unit of an antibody against CD19 (CAR-T cells) is the latest and most exciting of these engineered therapies，what’s the role and efficacy of CAR-T therapy in relapsed/refractorynon‐Hodgkin lymphoma (NHL) in adults?

 

　　Dr Levy: So far， CAR-T cells are made with an antibody that recognizes CD19. CD 19 is a target on many kinds of lymphoma including non-Hodgkin’s lymphoma (but not in Hodgkin’s disease) and acute lymphocytic leukemias typical of those seen in children. It works well in the leukemias as well as the lymphomas in some people， but not everyone.

 

　　Q3: Antibodies against the host immune system (i.e. PD1) are rapidly changing the field of cancer treatment and especially of Hodgkin’s Disease，what are the durable response rates of PD1 in relapsed/refractory patients.

 

　　Dr Levy: The response rates are 80% in Hodgkin’s disease patients who have failed all the other usual treatments. We are going to hear about the durations of response at this meeting and I think they are pretty good. About half of patients are relapsing in around one year. We would like it to be better than that though.

 

　　Q4: Combinations with existing targeted and chemotherapies are promising first-line options for lymphoma patients， what do you think of the application of this kind of therapies in clinical practice?

 

　　Dr Levy: So far， none of the combinations have been proven yet， but again we are going hear more about that at this meeting. Everyone is looking for the best combinations. PD-1 has been approved already and is effective in some people and we are all looking for a new combination with PD-1 that will make it work in a larger patient population. We have some good ideas， and we have some that have shown to not work， so we have a lot still to learn.

 

　　Q5: It seemsthat clever combinations of the new small molecule drugs and the immunotherapies will one day produce cures for cancer without the unpleasant side effects of our current therapies，what’ s your point of this trends in the field of lymphoma therapy?

 

　　Dr Levy: I think this is the future of the field. When we find the right combinations that are effective， they also should not cause more side effects. That is the tricky part. If the combination works better against the tumor， they may also have an impact on the patients’ normal tissue. So we are searching for combinations that work better against the tumor， but not causing more side effects.