Abstract: Described herein is a method for loading a hydrophilic compound into liposomes after addition of an alkylester group to form an esterified compound. After loading, the alkylester is hydrolyzed to reform the hydrophilic compound inside the liposomes. Also described is a method for loading drugs under a glucuronide methylester form into liposomes. The glucuronide methylester form of the drug is saponified to a glucuronide form of the drug inside the liposomes for better drug retention. The glucuronide residue conjugated to drugs can be removed inside cells to regenerate the parental drug upon cell uptake, liposomal degradation and enzyme hydrolysis. In case of cancer, this method can be used to safely deliver drugs to tumors.

Abstract: Described herein is a method for loading a hydrophilic compound into liposomes after addition of an alkylester group to form an esterified compound. After loading, the alkylester is hydrolyzed to reform the hydrophilic compound inside the liposomes. Also described is a method for loading drugs under a glucuronide methylester form into liposomes. The glucuronide methylester form of the drug is saponified to a glucuronide form of the drug inside the liposomes for better drug retention. The glucuronide residue conjugated to drugs can be removed inside cells to regenerate the parental drug upon cell uptake, liposomal degradation and enzyme hydrolysis. In case of cancer, this method can be used to safely deliver drugs to tumors.

Abstract: The invention relates to the synthesis of a second-generation camptothecin glucuronide prodrug (BQC-G) of a potent anticancer camptothecin derivative 5,6-dihydro-4H-benzo[de]quinoline-camptothecin (BQC). BQC-G was over 4000 times more water soluble than BQC, displayed good stability in human plasma and was an excellent substrate for enzymatic hydrolysis by bacterial and human ?-glucuronidases. BQC-G was about 30 times less toxic than BQC, but was as toxic as BQC after hydrolysis of the glucuronide moiety by ?-glucuronidase. In the presence of human serum albumin, BQC-G displayed lower cytotoxicity (IC50=1080 nM) but could be activated by ?-glucuronidase to display potent activity (IC50=13.3 nM).

Abstract: This disclosure relates to a method to mimicking the germinal center reaction to generate antibodies with altered binding properties or increased affinity directly in hybridomas. To allow convenient and rapid affinity maturation of antibodies, a controllable activation-induced cytidine deaminase (AID) expression system to induce somatic hypermutation in hybridomas is developed. Selection of high affinity antibodies is achieved by fluorescence-activated cell sorting of hybridomas that preferentially bind fluorescence-labeled antigens. The disclosure also relates to de novo generation of hybridomas with tunable antibody affinity by generating myeloma fusion partners with controllable AID expression.

Abstract: The invention provides a recombinant nucleotide sequence, including the sequence of SEQ ID No. 1, SEQ ID No. 2, SEQ ID No. 3 or SEQ ID No. 4, wherein the recombinant nucleotide sequence encodes an anti-polyethylene glycol recombinant single chain membrane antibody.

Abstract: The invention relates to the synthesis of a second-generation camptothecin glucuronide prodrug (BQC-G) of a potent anticancer camptothecin derivative 5,6-dihydro-4H-benzo[de]quinoline-camptothecin (BQC). BQC-G was over 4000 times more water soluble than BQC, displayed good stability in human plasma and was an excellent substrate for enzymatic hydrolysis by bacterial and human ?-glucuronidases. BQC-G was about 30 times less toxic than BQC, but was as toxic as BQC after hydrolysis of the glucuronide moiety by ?-glucuronidase. In the presence of human serum albumin, BQC-G displayed lower cytotoxicity (IC50=1080 nM) but could be activated by ?-glucuronidase to display potent activity (IC50=13.3 nM).

Abstract: The invention provides a recombinant nucleotide sequence, including the sequence of SEQ ID No. 1, SEQ ID No. 2, SEQ ID No. 3 or SEQ ID No. 4, wherein the recombinant nucleotide sequence encodes an anti-polyethylene glycol recombinant single chain membrane antibody.

Abstract: A chimeric protein expressed from a transgene tranduced into a mammalian tumor cell and method of using the chimeric protein for cancer treatment. The chimeric protein comprises an effector and an anchor, which are linked by a spacer. The chimeric protein, when expressed and exposed on the tumor cell surface in vivo can activate T cells, which further lead to lysis of the tumor cells. The anti-tumor effects can be enhanced by co-expression of certain co-stimulators, such as CD80 or CD86.