The mantle cell lymphoma (MCL) International Prognostic Index (MIPI) and combined MIPI (MIPI-c) are commonly used for risk classification of MCL patients. However, these indexes lack immune-related parameters. The purpose of this study was to develop a novel prognostic model that integrated clinical and immune parameters. A total of 189 patients with newly diagnosed MCL from January 2010 to June 2020 were enrolled in our study. A nomogram and immune-related prognostic index (IRPI) were established to predict the overall survival (OS) of patients according to univariate and multivariate analyses. Discrimination and calibration were used to compare the prognostic performance of the IRPI, MIPI, and MIPI-c. External validation was performed based on validation dataset (n = 150) from two other centers. The results for the training dataset indicated that B symptoms, platelet count, B2M level, CD4+ T-cell count<26.7% and CD8+ T-cell count>44.2% were predictors for OS. All the prognostic factors were integrated into the nomogram. For the overlap of confidence intervals of each variable, we assigned one point for each factor. The IRPI categorized patients into three risk categories: a score of zero indicated low risk, a score of one or two indicated intermediate risk, and a score of ≥3 indicated high risk. The IRPI showed better discrimination and calibration power than the MIPI and MIPI-c in the training dataset and validation dataset. The novel IRPI is a refined risk stratification index and reflects the strong complementary prognostic effects between clinical and immune parameters in MCL.

Background: Mantle cell lymphoma (MCL) is an aggressive B cell lymphoma with short median survival, ranging from 3 to 5 years. Immunochemotherapy is currently the standard approach for treating MCL patients. For optimization of the treatment, an ideal drug delivery system would improve the biological effectiveness and reduce the treatment-related toxicity. Exosome are small vesicles with 30-150 nm in diameter, released from various types of cells. It serves as a messenger transmitter between cells and exhibits a large potential for drug delivery. In current study, we developed a chimeric antigen receptor engineered exosome (CAR-Exo) consisting of membrane fused anti-CD19 scFv. We sought to use this exosome as a drug delivery system for targeting MCL cell in vitro and in vivo .

B-acute lymphoblastic leukemia (B-ALL) is derived from B cell progenitors. Recently, the development of appropriate combinations of chemotherapy and immunotherapy represents a promising approach for eliminating cancer. We previously constructed an anti-CD3 × anti-CD19 bi-specific antibody in a diabody configuration and its disulfide-stabilized format (ds-diabody). The combination of the diabody or ds-diabody and Ara-C was highly effective in enhancing the cytotoxicity of T cells against the CD19+ human leukemia cell-line, Nalm-6, both in vitro and in vivo. This study verified whether B-ALL patient-derived cells were sensitive to the diabody or ds-diabody and low-dosage Ara-C combination.

Chemotherapeutic drugs can enhance an immune response of the host against the tumor in addition to killing cancer cells by direct cytotoxicity. Therefore, the combination of chemotherapy and immunotherapy is a promising approach for eliminating tumors, particularly in advanced stages. A strategic medication is to use a bispecific antibody format that is capable of recruiting polyclonal T cells around antibody-target-expressing tumor cells. Recently, we have constructed a bispecific antibody, anti-CD3 x anti-CD19, in a diabody configuration. In this study, we measured B7 family members B7.1 (CD80) and B7.2 (CD86) expressed on a CD19(+) human leukemia cell line, Nalm-6, stimulated by cytosine arabinoside (Ara-C). We found that a low concentration of Ara-C could upregulate CD80 expressed on CD19(+) Nalm-6 cells. The cytotoxicity of T lymphocytes against Nalm-6 cells in vitro and in vivo mediated by the anti-CD3 x anti-CD19 diabody with or without a low dose of Ara-C was compared. The combination of the anti-CD3 x anti-CD19 diabody and Ara-C showed the greatest effectiveness in enhancing the cytotoxicity of T cells against the tumor cells in vitro and in vivo. Activated T cells expressed higher levels of CD25 and CD69 and released more interleukin 2. Both perforin/granzyme B system and Fas/FasL pathway were involved in the diabody-induced T-cell cytotoxicity. Moreover, the activated T cells could upregulate ICAM-3 expression on Nalm-6 cells, and inhibition of LFA-1-ICAM-3 interaction impaired cytotoxicity of T cells. It was noted that Ara-C could upregulate CD80 expressed on two of five specimens of acute B lymphoblastic leukemia patient-derived cells. Cytotoxicity of T cells against these two patient-derived cells was enhanced in the presence of the anti-CD3 x anti-CD19 diabody. These findings indicate that treatment strategy using both cytotoxic lymphocyte-based immunotherapy and chemotherapy may have synergistic effects.

We present a rare case of concurrent medullary thyroid cancer (MTC) and relapse of Graves' disease (GD).A 26-year-old Chinese female suffered from GD for 1 year.Physical examination demonstrated mildly diffuse goiter with a palpable 1.0 cm nodule in the right thyroid lobe and exophthalmos.Before hemithyroidectomy, calcitonin was elevated and thyroglobulin was normal.After surgery, histopathological fi ndings proved coexistence of MTC and GD.16 months later, GD relapsed and radioactive iodine 131 therapy was given.Meanwhile, postoperative monitoring showed well controlled calcitonin and carcinoembryonic antigen.Our lesson demonstrates although concomitant of MTC and GD is very rare, yet after hemithyroidectomy for the single nodular MTC lesion, remnant thyroid lobe could be the source of GD relapse very soon.More importantly, the relapse of GD and the following radioiodine therapy and radiation exposure could have been prevented if a better therapy plan of total thyroidectomy was adopted in the fi rst place, instead of hemithyroidectomy (Tab. 1, Fig. 2, Ref. 11).

Background A diabody is a bispecific antibody that is capable of recruiting a polyclonal T cell to antibody target-expressing tumor cells. However, the two chains of diabodies tend to dissociate because they are integrated non-covalently. Therefore, it is necessary to remodel the diabody to increase its stability in order to enhance the antitumor activity. Methods We constructed an antiCD3×antiCD19 diabody with one binding site for the T cell antigen receptor (TCRCD3) and the other for the B cell-specific antigen (CD19) by recombinant gene engineering technology. Cysteine residues were introduced into the V domains of the anti-CD3 segment. The stability and cytotoxicity of the two diabodies were compared in vitro and vivo. Results The disulfide-stabilized (ds) diabodies produced by Escherichia coli were secreted with high yields in a fully active form without a decrease in affinity. Compared with the parental diabody, the disulfide-stabilized (ds) diabody proved more stable in vitro and in vivo without reducing binding affinity. Both were able to effectively eliminate human lymphoma Raji cells by redirecting T lymphocytes in vitro and in vivo, but the ds diabody was more effective in inhibiting the growth of xenografts transplanted in BALB/C nude mice. Conclusion The antiCD3×antiCD19 ds diabody is more suitable for a controlled polyclonal T cell therapy of human CD19-positive B cell malignancies than its parental diabody.

BACKGROUND & OBJECTIVE:Gefitinib, a selective inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase, has been approved to be used in treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) in many countries. This study, a multicenter clinical trial, was designed to evaluate the efficacy of gefitinib on Chinese patients with locally advanced or metastatic NSCLC after failure of previous chemotherapy, and explore its safety.METHODS:A total of 159 pathologically-confirmed NSCLC patients were enrolled. Gefitinib was orally administered 250 mg once daily until disease progression or the occurrence of intolerable toxicity.RESULTS:The objective response rate was 27.0%; the disease control rate was 54.1%. The median progression-free survival time was 97 days; the median overall survival time was 10.0 months; the 1-year survival rate was 44%. The most common drug-related adverse events were rash (44.0%), pruritus (15.7%), and diarrhea (10.1%), and most of them were grade 1-2 events with no need of further treatment.CONCLUSION:Gefitinib is effective and safe in treating Chinese patients with locally advanced or metastatic NSCLC after failure of previous chemotherapy.