研制出美罗华的斯坦福实验室再添新成果，目前正在招募

魔都小曹 · 发表于 2020-12-12 19:07:16

本帖最后由魔都小曹于 2020-12-13 10:48 编辑

我们体内的免疫细胞具有消除肿瘤的作用，但在面对癌细胞时，它需要一个催化剂或一种刺激才能完成这项使命。而当前的免疫疗法主要通过刺激整个身体的免疫系统来促使免疫细胞消灭肿瘤；靶向治疗通常针对限制肿瘤细胞活性的免疫细胞。大热的CAR-T细胞治疗则需要将患者体内的免疫细胞提取至体外，经过处理后再回输至体内用以攻击肿瘤细胞。 无论是哪一种方法，如今都面临着高昂的成本及长时间的准备和处理等缺陷。2018年1月31日发表在《Science Translational Medicin》上名为“Eradication of spontaneous malignancy by local immunotherapy” 的研究中，斯坦福大学医学院的研究人员成功的 将微量的两种免疫刺激剂注射到小鼠的实体瘤中，并有效的消除了小鼠体内所有的癌症痕迹！甚至包括远端未经处理的转移病灶！

同时，局部应用少量药物作为一种快速且相对便宜的癌症治疗，也不太会导致全身免疫刺激常见的不良副作用。而该实验方法也不限于癌症的种类，可适用于多种不同类型的癌症，其中也包括自发性癌症。

抗癌中的“黄金搭档”

研究人员在小鼠腹部的两个不同位置分别插入癌细胞，以此诱发肿瘤。当肿瘤细胞存活并开始生长后，注入多种拥有抗癌能力、可激活免疫细胞的抗体分子到每只小鼠的肿瘤内。通过观察这些肿瘤的反应，被实验的20种分子内的两种分子蛋白引起了他们的注意： 抗免疫细胞蛋白OX40的抗体分子和CpG的寡核苷酸短DNA片段。

OX40抗体能激活T细胞并引起对癌细胞的抵抗和攻击。而CpG的寡核苷酸短DNA则可与附近的免疫细胞一共工作，增加了T细胞表面OX40抗体的表达。

不过值得注意的是，这两种分子必须合作才能发挥作用，如果只注射其中一种，效果则会大打折扣。

乳腺癌中大展拳脚

当发现这一对分子组合后，研究人员立即在乳腺癌的小鼠模型上进行了试验。将这对分子联合注入有两个肿瘤部位的小鼠的某一个肿瘤后。结果显示，不仅仅是被注射的肿瘤开始退化，另一个没有经过注射的肿瘤也表现出了退化的迹象。

在实验的90只小鼠中有87只都被治愈！而另外3只肿瘤复发的小鼠，在经过第二次的治疗后，肿瘤都再次开始消退！

在随后的结肠癌和黑色素瘤的小鼠模型中也出现了相同的实验结果。

同时，研究人员发现，治疗第一个出现的肿瘤往往可以预防未来肿瘤的发生，并显著增加小鼠的寿命。

斯坦福大学的医学肿瘤学家Ron Levy推测，这种特殊的分子组合同样适用于癌症患者。联合治疗除了消除被注射的肿瘤外，还会破坏其他肿瘤，甚至能抑制肿瘤转移，消灭癌症扩散后的继发肿瘤。

在即将展开的临床试验中，研究人员将招募15名低度恶性淋巴瘤患者。如果试验成功，该方法将在更多不同类型的肿瘤患者上进行测试。

或许我们可以假设，未来临床医生就能在手术切除癌症之前用这种方法抑制癌细胞的转移和复发，甚至预防由BRCA1和2基因突变可能引起的癌症。

上面是转载的，为了避免是不属实消息，我去看了一下教授的斯坦福官网主页，发现还在招募...低级别b细胞非霍奇金淋巴瘤...有兴趣有能力的可以去试下，反正副作用好像也不大

招募网址

https://clinicaltrials.stanford.edu/browse-all-trials.html?ctid=NCT034109010

TLR9 Agonist SD-101, Anti-OX40 Antibody BMS 986178, and Radiation Therapy in Treating Patients With Low-Grade B-Cell Non-Hodgkin Lymphomas

This phase I trial studies the side effects and best dose of the anti-OX40 antibody BMS-986178 when given together with the TLR9 agonist SD-101 and radiation therapy in treating patients with low-grade B-cell Non-Hodgkin lymphomas. TLR9 agonist SD-101 may stimulate the immune system in different ways and stop cancer cells from growing. Anti-OX40 antibody is a monoclonal antibody that enhances the activation of T cells, immune cells that are important for fighting tumors Radiation therapy uses high energy x-rays to kill cancer cells and may make them more easily detected by the immune system. Giving TLR9 agonist SD-101 together with anti-OX40 antibody BMS 986178 and radiation therapy may work better in treating patients with low-grade B-cell non-hodgkin lymphomas.

Stanford is currently accepting patients for this trial.

Lead Sponsor:

Ronald Levy

Collaborator: National Cancer Institute (NCI)

Stanford Investigator(s):

Michael Khodadoust

Richard Hopp

Ronald Levy, MD

Intervention(s):

Biological: Anti-OX40 Antibody BMS 986178 Other: Laboratory Biomarker Analysi Radiation: Radiation Therapy Drug: TLR9 Agonist SD-101

Eligibility

Inclusion Criteria:

-  Biopsy confirmed low-grade B-cell lymphoma, excluding gastric MALT lymphoma, high-risk
mantle cell lymphoma, and currently transformed lymphoma

-  Patients must have at least one site of disease (cervical, axillary, inguinal, or
subcutaneous) that is accessible for intratumoral injection of SD-101 (diameter ≥10mm)
percutaneously and presents a low risk for complications from direct injections.

-  Patients must have at least one site of measurable disease, other than the injection
site, which is not included in the radiation field

-  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

-  Absolute neutrophil count (ANC) >= 1000/mm^3 independent of growth factor support

-  Platelets: >= 100,000/mm^3 or >= 50,000/mm^3 if known or suspected bone marrow
involvement, independent of transfusion support in either situation

-  Hemoglobin: >= 8 g/dL (may be transfused)

-  Creatinine: Creatinine clearance > 25 ml/min

-  Aspartate aminotransferase (AST)/alanine aminotransferase (ALT): =< 3 x upper limit of
normal (ULN)

-  Bilirubin: =< 1.5 x ULN (except for subjects with Gilbert's Syndrome or of non-hepatic
cause)

-  Must be at least 4 weeks since treatment with standard or investigational
chemotherapy, biochemotherapy, surgery, radiation, cytokine therapy, any monoclonal
antibodies or immunotherapy, and recovered from any clinically significant toxicity
experienced during treatment

-  Women of childbearing potential and men who are sexually active must be practicing a
highly effective method of birth control during and after the study consistent with
local regulations regarding the use of birth control methods for subjects
participating in clinical trials; men must agree to not donate sperm during and after
the study; for sexually active women of childbearing potential, these restrictions
apply for 5 months after the last dose of study drug; for sexually active men, these
restrictions apply for 7 months after the last dose of study drug

-  Women of childbearing potential must have a negative serum (beta-human chorionic
gonadotropin [beta-hCG]) or urine pregnancy test at screening, within 24 hours of the
first dose of anti-OX40 antibody, and every four weeks while on study treatment; women
who are pregnant or breastfeeding are ineligible for this study

-  Life expectancy greater than 3 months

-  Ability to comply with the treatment schedule

-  Ability to understand and willingness to sign a written informed consent document

Exclusion Criteria:

-  Currently transformed lymphoma, high-risk mantle cell lymphoma, or gastric MALT
lymphoma.

-  Need for immediate treatment or cytoreduction.

-  No easily accessible site for direct percutaneous injection with low-risk for
potential complications.

-  Autoimmune disease requiring treatment within the last 5 years including systemic
lupus erythematosus, rheumatoid arthritis, multiple sclerosis, Sjogren's syndrome,
autoimmune thrombocytopenia, uveitis, or other if clinically significant

-  Major surgery within 4 weeks of enrollment, or a wound that has not fully healed

-  Vaccinated with live, attenuated vaccines within 4 weeks of enrollment

-  Known history of human immunodeficiency virus (HIV) or active hepatitis C virus or
active hepatitis B virus infection or any uncontrolled active systemic infection

-  Known central nervous system (CNS) lymphoma

-  Patients with a history of prior malignancy with the exception of non-melanoma skin
cancer, carcinoma in situ of the cervix, in situ carcinoma of the bladder, or other
malignancy that has undergone potentially curative therapy with no evidence of disease
for the last > 2 years and that is deemed by the investigator to be a low risk for
recurrence

-  History of significant allergic reactions attributed to compounds of similar
composition to SD-101 or BMS-986178

-  Treatment with an immunosuppressive regimen of corticosteroids or other
immunosuppressive medication (e.g., methotrexate, rapamycin) within 30 days of study
treatment; Note: patients may take up to 5 mg of prednisone or equivalent daily;
topical and inhaled corticosteroids in standard doses are allowed

-  Significant cardiovascular disease (i.e. New York Heart Association [NYHA] class 3
congestive heart failure; myocardial infarction within the past 6 months; unstable
angina; coronary angioplasty with the past 6 months; uncontrolled atrial or
ventricular cardiac arrhythmias)

-  Pregnant or breast feeding

-  Any other medical history, including laboratory results, deemed by the investigator
likely to interfere with their participation in the study, or to interfere with the
interpretation of the results

Ages Eligible for Study 18 Years - N/A

Genders Eligible for Study All

觉得做出美罗华的实验室应该挺靠谱的吧...真的希望未来多点希望,,,https://clinicaltrials.gov/ct2/show/NCT03410901?cond=Low-grade+B+Cell+Non-Hodgkin%27s+Lymphoma&draw=2&rank=3 这个是临床的链接，使用了放疗加双药，其实我觉得不出于实验目的，用美罗华单药加两个药一样可以吧,,,