Heryanto Yusri-Dwi, Hanaoka Hirofumi, Nakajima Takahito, Yamaguchi Aiko, Tsushima Yoshito
Department of Diagnostic Radiology and Nuclear Medicine, Gunma University Graduate School of Medicine, 39-22 Showa-machi 3-chome, Maebashi, 371-8511, Japan.
Department of Bioimaging Information Analysis, Gunma University Graduate School of Medicine, 39-22 Showa-machi 3-chome, Maebashi, 371-8511, Japan.
Ann Nucl Med. 2017 Nov;31(9):669-677. doi: 10.1007/s12149-017-1197-9. Epub 2017 Jul 24.
Radioimmunotherapy (RIT) has proven effective for patients with relapsed and refractory lymphoma. However, new types of therapy are strongly desired as B-cell lymphoma remains incurable for many patients. Photoimmunotherapy (PIT) is an emerging targeted cancer therapy that uses photosensitizer (IR700)-conjugated monoclonal antibodies (mAbs) to specifically kill cancer cells. To evaluate the usefulness and potential role of PIT for treating B-cell lymphoma in a comparison with RIT, we performed in vivo PIT and RIT studies with an IR700 or Y-conjugated anti-CD20 mAb, NuB2.
IR700 or Y were conjugated to NuB2. Since cell aggressiveness greatly affects the therapeutic effect, we selected both an indolent (RPMI 1788) and an aggressive (Ramos) type of B-cell lymphoma cell line. The in vitro therapeutic effect of PIT and the biodistribution profiles of IR700-NuB2 were evaluated. In vivo PIT and RIT studies were performed with 100 or 500 μg of IR700-NuB2 and 150 μCi/20 μg of Y-NuB2, respectively, in two types of B-cell lymphoma-bearing mice.
The in vitro studies revealed that Ramos was more sensitive than RPMI 1788 to PIT. The therapeutic effect of PIT with 500 µg IR700-NuB2 was superior to any other therapies against aggressive Ramos tumors, whereas RIT showed the highest therapeutic effect in indolent RPMI 1788 tumors. Since the uptake levels and intratumoral distribution of IR700-NuB2 were comparable in both tumors, a possible cause of this difference is the tumor growth rate. The PIT with 500 µg (IR700-NuB2) group showed a significantly greater therapeutic effect than the PIT with 100 µg group due to the higher and more homogeneous tumor distribution of IR700-NuB2.
PIT was effective for both indolent and aggressive B-cell lymphoma, and the higher dose provided a better therapeutic effect. In aggressive tumors, PIT was more effective than RIT. Thus, PIT would be a promising strategy for the locoregional treatment or control of B-cell lymphoma. Since PIT and RIT have distinctive advantages over each other, they could play complementary rather than competitive roles in B-cell lymphoma treatment.
放射免疫疗法（RIT）已被证明对复发难治性淋巴瘤患者有效。然而，由于许多患者的B细胞淋巴瘤仍无法治愈，因此迫切需要新型疗法。光免疫疗法（PIT）是一种新兴的靶向癌症疗法，它使用与光敏剂（IR700）偶联的单克隆抗体（mAb）来特异性杀死癌细胞。为了评估PIT与RIT相比在治疗B细胞淋巴瘤中的有效性和潜在作用，我们使用与IR700或Y偶联的抗CD20 mAb NuB2进行了体内PIT和RIT研究。
将IR700或Y与NuB2偶联。由于细胞侵袭性对治疗效果有很大影响，我们选择了一种惰性（RPMI 1788）和一种侵袭性（Ramos）类型的B细胞淋巴瘤细胞系。评估了PIT的体外治疗效果和IR700-NuB2的生物分布情况。分别用100或500μg的IR700-NuB2和150μCi/20μg的Y-NuB2在两种荷B细胞淋巴瘤小鼠中进行体内PIT和RIT研究。
体外研究表明，Ramos对PIT比RPMI 1788更敏感。500μg IR700-NuB2的PIT治疗效果优于针对侵袭性Ramos肿瘤的任何其他疗法，而RIT在惰性RPMI 1788肿瘤中显示出最高的治疗效果。由于IR700-NuB2在两种肿瘤中的摄取水平和瘤内分布相当，这种差异的一个可能原因是肿瘤生长速度。500μg（IR700-NuB2）组的PIT由于IR700-NuB2在肿瘤中的分布更高且更均匀，其治疗效果明显优于100μg组。
PIT对惰性和侵袭性B细胞淋巴瘤均有效，较高剂量可提供更好的治疗效果。在侵袭性肿瘤中，PIT比RIT更有效。因此，PIT将是局部治疗或控制B细胞淋巴瘤的一种有前景的策略。由于PIT和RIT彼此具有独特的优势，它们在B细胞淋巴瘤治疗中可能发挥互补而非竞争的作用。
