Highly specific auto-antibodies against claudin-18 isoform 2 induced by a chimeric HBcAg virus-like particle vaccine kill tumor cells and inhibit the growth of lung metastases.

Strategies for antibody-mediated cancer immunotherapy, such as active immunization with virus-like particle (VLP)-based vaccines, are gaining increasing attention. We developed chimeric hepatitis B virus core antigen (HBcAg)-VLPs that display a surface epitope of the highly selective tumor-associated cell lineage marker claudin-18 isoform 2 (CLDN18.2) flanked by a mobility-increasing linker. Auto-antibodies elicited by immunization with these chimeric HBcAg-VLPs in 2 relevant species (mouse and rabbit) bind with high precision to native CLDN18.2 at physiologic densities on the surface of living cells but not to the corresponding epitope of the CLDN18.1 splice variant that differs by merely one amino acid. The induced auto-antibodies are capable of efficiently killing CLDN18.2 expressing cells in vitro by complement-dependent and antibody-dependent cell-mediated cytotoxicity. Moreover, they provide partial protective immunity against the challenge of mice with syngeneic tumor cells stably expressing CLDN18.2. Our study provides a first proof-of-concept that immunization combining VLPs as antigen carriers with specific conformational epitopes of a highly selective differentiation antigen may elicit auto-antibodies with high cytocidal and tumoricidal potential.

Defining subclinical keratoconus using corneal first-surface higher-order aberrations.

PURPOSE: To describe corneal higher-order wavefront aberrations of clinically inconspicuous fellow eyes in patients with early keratoconus (KC). DESIGN: Prospective comparative case series, conducted at a university eye hospital outpatient clinic. METHODS: Twenty-three eyes (group 1) were newly diagnosed with KC; 10 eyes (group 2) were asymptomatic fellow eyes that showed neither major topographic anomaly nor clinical signs of KC; 127 healthy eyes of 74 patients served as negative controls (group 3). A seventh-order Zernike decomposition of first-surface aberrations was performed. Single Zernike coefficients, higher-order aberration root mean square (HOA RMS) values, the Z3 index and the output values of discriminant analysis D(13) (with input from groups 1 and 3) and D(23) (groups 2 and 3) were assessed for their usefulness to discriminate between clinically normal fellow eyes, KC eyes and controls by plotting receiver-operating characteristic (ROC) curves. RESULTS: There were significant differences between group 1 and group 3 for 11 Zernike coefficients, Z3, total HOA RMS, coma RMS and third-order RMS. Group 2 and 3 showed significant differences only for the coefficients Z(3)(-1) and Z(5)(-1). Z(3)(-1), D(13), and D(23) discriminated between groups 1 and 3 with maximum sensitivity and specificity. For discrimination between groups 2 and 3, D(23) turned out to be the best parameter (A(z) ROC = 0.98), followed by Z(3)(-1) (A(z) ROC = 0.96). CONCLUSIONS: Clinically normal fellow eyes of eyes with early KC showed significant differences of first-surface aberrations compared to normal eyes and could therefore be considered as eyes with subclinical KC.

Influence of pupil and optical zone diameter on higher-order aberrations after wavefront-guided myopic LASIK.

PURPOSE: To investigate the influence of pupil and optical zone (OZ) diameter on higher-order aberrations (HOAs) after myopic wavefront-guided laser in situ keratomileusis (LASIK). METHODS: Twenty-seven myopic eyes of 19 patients were included. The mean preoperative spherical equivalent was -6.86 diopters (D) +/- 1.24 (SD) (range -4.25 to -9.5 D); the mean planned OZ diameter was 6.26 +/- 0.45 mm (range 5.7 to 7.1 mm). All patients had uneventful wavefront-guided LASIK (Zyoptix version 3.1, Bausch & Lomb) and an uncomplicated follow-up of 12 months. Wavefront measurements were performed with a Hartmann-Shack sensor in maximum mydriasis preoperatively and 12 months after LASIK. Wavefront errors were computed for pupil diameters (PDs) of 3.0, 3.5, 4.0, 5.0, 6.0, and 7.0 mm for the individual OZ diameter and for the individual mydriatic PD (7.93 +/- 0.46 mm). The impact of the relationship between pupil diameter and OZ diameter (fractional clearance [FC]) on HOA was described and quantified using curvilinear regression with a 4th-order polynomial fit. RESULTS: There was a reproducible relationship between FC and the amount of induced HOA. The change in HOA root mean square and primary spherical aberration (Z(4)0) was significantly correlated with FC. If the OZ was 16.5% larger than the pupil (FC = 1.17), only half the amount of HOA was expected to be induced than if the OZ equaled the pupil. In contrast, an OZ that was 9% smaller than the pupil (FC = 0.91) resulted in an HOA induction 50% higher than at FC = 1. CONCLUSION: The OZ zone to pupil ratio (fractional clearance) had a significant impact on HOA induction after wavefront-guided LASIK.

Wavefront-guided LASIK with the Zyoptix 3.1 system for the correction of myopia and compound myopic astigmatism with 1-year follow-up: clinical outcome and change in higher order aberrations.

OBJECTIVE: To assess safety, efficacy, predictability, stability, and change in aberrations after wavefront-guided LASIK for myopia and myopic astigmatism. DESIGN: Prospective, nonrandomized, self-controlled trial. PARTICIPANTS: Wavefront-guided LASIK was performed in 97 eyes in a 1-year trial. Treated eyes had a mean subjective manifest spherical equivalent (SE) of -5.22+/-2.07 diopters (D), with a range of -0.25 to -9.00 D of myopia and 0 to -3.25 D of astigmatism. INTERVENTION: After a microkeratome cut, a wavefront-based excimer ablation (Zyoptix 3.1) was performed. The full treatment to achieve emmetropia of an early nomogram provided by the system manufacturer was used in all procedures. MAIN OUTCOME MEASURES: Safety, efficacy, predictability, and stability were evaluated at 1, 3, and 12 months postoperatively. Wavefront changes of higher order aberrations (HOAs) at 1 year were determined for pupil sizes of 3.5 and 6 mm. RESULTS: At 1 year postoperatively, uncorrected visual acuity (VA) was 20/20 or better in 83% of the eyes, and 20/40 or better in 98%. The mean subjective manifest SE at 1 year was -0.25+/-0.43 D; it was within 0.50 D in 77% and within 1.0 D in 95%. No eye lost > or =2 lines of best spectacle-corrected VA (BSCVA) at 1 year postoperatively; 40 eyes gained 1 line of BSCVA, and 5 eyes gained 2 lines. The total HOA root mean square (RMS) increased on average by a factor of 1.23+/-0.57 with a 3.5-mm pupil; for the 6 mm pupil, the increase factor was 1.52+/-0.36. No change or reduction in the total HOA RMS was observed in 45.5% of the eyes for a 3.5-mm pupil and in 20.6% for a 6-mm pupil. There was a significant increase of primary spherical aberration (Z 4,0) by a factor of 4.11+/-10.17 for 3.5-mm pupils and 4.31+/-6.76 for 6-mm pupils. CONCLUSIONS: Wavefront-guided LASIK using Zyoptix 3.1 is an effective and safe procedure for the treatment of myopia and myopic astigmatism. Although in close to half of the eyes HOAs could be reduced, there was still undercorrection and induction of HOAs with the algorithm employed.